lets source our gene functions for extracting the top 25 genes and also for returning the mean and median fold change values from the Uterine Leiomyoma and the flu immunization samples after 1 and 7 days.
This will read in the tables and the functions from our earlier scripts, geneCardsDataGrab2.Rmd file we made into geneCards.R as a source.
source("geneCards.R")library(rvest)
library(lubridate)
library(dplyr)I want to look at some other human body network genes involved in process systems and body functions like serous fluid in the body cavities of the pericardium, pleural cavity, and pericardium of the heart, lung, and abdomen/pelvis respectively. Also, the clast and blast cells of the connective tissue that destroy old, damaged tissue or build and repair tissue respectively in the connective tissue. Connective tissue is the ligaments, tendons, fascia, blood, lymph, and cartilage. The blood connective tissue consists of erythrocytes (transport oxygen and carbon dioxide to cells), leukocytes that are the antibodies or white blood cells, the thrombocytes for blood clotting abilities to seal cuts and wounds and prevent bleeding out, and plasma to transport blood in the body.
Lets start with the serous fluid genes.
Serous fluid for UL:
find25genes('serous fluid')getProteinGenes('serous fluid')serousGenes <- read.csv('Top25serous-fluids.csv', header=T,sep=',', na.strings=c('',' ','NA'), stringsAsFactors = F)
serousGenes## proteinType proteinSearched todaysDate
## 1 TP53 serous-fluid Tue Aug 04 12:07:14 2020
## 2 TNF serous-fluid Tue Aug 04 12:07:14 2020
## 3 IL10 serous-fluid Tue Aug 04 12:07:14 2020
## 4 BRCA1 serous-fluid Tue Aug 04 12:07:14 2020
## 5 IL1B serous-fluid Tue Aug 04 12:07:14 2020
## 6 PIK3CA serous-fluid Tue Aug 04 12:07:14 2020
## 7 BRCA2 serous-fluid Tue Aug 04 12:07:14 2020
## 8 KRAS serous-fluid Tue Aug 04 12:07:14 2020
## 9 IFNG serous-fluid Tue Aug 04 12:07:14 2020
## 10 ERBB2 serous-fluid Tue Aug 04 12:07:14 2020
## 11 PTEN serous-fluid Tue Aug 04 12:07:14 2020
## 12 IL6 serous-fluid Tue Aug 04 12:07:14 2020
## 13 CCL2 serous-fluid Tue Aug 04 12:07:14 2020
## 14 AKT1 serous-fluid Tue Aug 04 12:07:14 2020
## 15 CTNNB1 serous-fluid Tue Aug 04 12:07:14 2020
## 16 BRAF serous-fluid Tue Aug 04 12:07:14 2020
## 17 MUC1 serous-fluid Tue Aug 04 12:07:14 2020
## 18 CDH1 serous-fluid Tue Aug 04 12:07:14 2020
## 19 APOE serous-fluid Tue Aug 04 12:07:14 2020
## 20 HRAS serous-fluid Tue Aug 04 12:07:14 2020
## 21 VEGFA serous-fluid Tue Aug 04 12:07:14 2020
## 22 CFH serous-fluid Tue Aug 04 12:07:14 2020
## 23 NRAS serous-fluid Tue Aug 04 12:07:14 2020
## 24 AFP serous-fluid Tue Aug 04 12:07:14 2020
## 25 CXCL8 serous-fluid Tue Aug 04 12:07:14 2020for (i in serousGenes$proteinType){
getSummaries(i,'serous fluid')
}getGeneSummaries('serous fluid')Lets look at the fold change values of these genes listed as more important in serous fluid.
getMeanMedian('TP53')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.418934 1.054537
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.348975 1.113545## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 1274 161.6 182.3 113.8 151.1 142.1 150.18
## 10723 67.0 59.5 43.6 35.8 18.4 44.86
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 1274 150.64 1.418934 1.348975
## 10723 44.23 1.054537 1.113545
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 1274 120.3 70.0 103.8 117.5
## 10723 63.2 27.3 53.7 36.9
## GSM9102 _nonUL mean _nonUL median _nonUL
## 1274 117.6 105.84 111.67
## 10723 31.6 42.54 39.72TP53 is over expressed by 5-41% more in UL samples than non-UL samples approximately. How about in the flu 1 day immunization samples.
getMeanMedianFlu1('TP53')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## numeric(0)
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## numeric(0)## [[1]]
## [1] Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## [3] Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day
## [5] median _flu_1day FoldChange_mean _flu_1day
## [7] FoldChange_median _flu_1day
## <0 rows> (or 0-length row.names)
##
## [[2]]
## [1] Flu.non.immunized.healthy _healthyNonImmz
## [2] Flu.non.immunized.healthy.1 _healthyNonImmz
## [3] Flu.non.immunized.healthy.2 _healthyNonImmz
## [4] Flu.non.immunized.healthy.3 _healthyNonImmz
## [5] Flu.non.immunized.healthy.4 _healthyNonImmz
## [6] Flu.non.immunized.healthy.5 _healthyNonImmz
## [7] mean _healthyNonImmz
## [8] median _healthyNonImmz
## <0 rows> (or 0-length row.names)Nothing was available in the 1 day flu immunization samples. It will likely be the same for 7 day unless some other error. They have the exact genes available in that data frame derived.
getMeanMedianFlu7('TP53')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## numeric(0)
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## numeric(0)## [[1]]
## [1] Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## [3] Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day
## [5] median _flu_7day FoldChange_mean _flu_7day
## [7] FoldChange_median _flu_7day
## <0 rows> (or 0-length row.names)
##
## [[2]]
## [1] Flu.non.immunized.healthy _healthyNonImmz
## [2] Flu.non.immunized.healthy.1 _healthyNonImmz
## [3] Flu.non.immunized.healthy.2 _healthyNonImmz
## [4] Flu.non.immunized.healthy.3 _healthyNonImmz
## [5] Flu.non.immunized.healthy.4 _healthyNonImmz
## [6] Flu.non.immunized.healthy.5 _healthyNonImmz
## [7] mean _healthyNonImmz
## [8] median _healthyNonImmz
## <0 rows> (or 0-length row.names)Now lets look at the next listed serous fluid gene, TNF:
getMeanMedian('TNF')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.9961014
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.010152## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 6639 43.4 35.9 42.7 33.4 49 40.88
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 6639 41.79 0.9961014 1.010152
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 6639 47.2 41.7 28 61.5 26.8
## mean _nonUL median _nonUL
## 6639 41.04 41.37There was only 1 gene in the UL data frame and the change was plus or minus 1% change, seems negligible.
Now, the 1 day flu immunizations:
getMeanMedianFlu1('TNF')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 1.07854
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 1.161913## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 11330 6.130804 8.941494
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 11330 7.152495 7.408264 7.28038
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 11330 1.07854 1.161913
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 11330 4.389836
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 11330 4.684353
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 11330 4.16446
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 11330 10.57719
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 11330 11.13105
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 11330 6.265858 6.868791
## median _healthyNonImmz
## 11330 6.265858The flu 1 day immunized samples were 8-16 % up regulated of over expressed than the healthy non-immunized flu samples.
Now for the 7 day flu immunized samples:
getMeanMedianFlu7('TNF')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 1.379212
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 1.510093## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 11330 10.16908 8.800952
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 11330 9.450532 9.473522 9.462027
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 11330 1.379212 1.510093
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 11330 4.389836
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 11330 4.684353
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 11330 4.16446
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 11330 10.57719
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 11330 11.13105
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 11330 6.265858 6.868791
## median _healthyNonImmz
## 11330 6.265858The 7 day flu immunized samples showed a drastic increase in TNF gene expression in the flu immunized samples of 37-51% compared to non-immunized healthy samples.
The third gene is IL10, lets see the results of this gene in UL samples:
getMeanMedian('IL10')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.9000719
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.9445245## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 6955 40.8 4.7 27.4 16.2 36.1 25.04
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 6955 26.22 0.9000719 0.9445245
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 6955 37.1 27.7 25.8 10.9 37.6
## mean _nonUL median _nonUL
## 6955 27.82 27.76The IL10 gene is about 10 % down regulated or under expressed in UL samples compared to non-UL samples.
Now in the 1 day flu immunized samples for IL10:
getMeanMedianFlu1('IL10')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9151371
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9113448## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 5068 2.698987 2.873398
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 5068 2.592244 2.721543 2.710265
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 5068 0.9151371 0.9113448
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5068 3.045313
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5068 3.073922
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5068 3.916677
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5068 2.552231
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5068 2.596116
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5068 2.659251 2.973918
## median _healthyNonImmz
## 5068 2.973918This gene IL10 is also down regulated approximately 10% in 1 day flu immunized samples compared to healthy non-immunized.
And now for the 7 day flu immunized samples IL10 fold change values:
getMeanMedianFlu7('IL10')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.9590879
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.9599085## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 5068 2.704722 2.994895
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 5068 2.85713 2.852249 2.854689
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 5068 0.9590879 0.9599085
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5068 3.045313
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5068 3.073922
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5068 3.916677
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5068 2.552231
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5068 2.596116
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5068 2.659251 2.973918
## median _healthyNonImmz
## 5068 2.973918IL10 is expressed half as much as the UL and 1 day immunized samples. At about 5% less in 7 day flu immunized samples compared to non-immunized and healthy samples.
The fourth gene is BRCA1, this is a cancer gene associated with estrogen and breast cancer. But lets look up the gene summary. Our file of gene summaries was created earlier but not read in, proteinGeneSummaries_serous-fluid.csv.
serousSumms <- read.csv('proteinGeneSummaries_serous-fluid.csv', sep=',',
header=T, na.strings=c('',' ','NA'),stringsAsFactors = F)
brca1 <- subset(serousSumms,serousSumms$gene=='BRCA1')
brca1$EntrezSummary## [1] "This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]"We can see that this gene is a tumor suppressor. Not necessarily that it is a cancer marker, but is used in breast cancer detection.
Lets see the gene expression of BRCA1 in UL samples:
getMeanMedian('BRCA1')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 2.174475 1.282200
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 2.173516 1.481106## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 4058 6.8 38.7 26.7 30.2 32.2 26.92
## 11245 22.4 23.4 40.6 45.7 45.1 35.44
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 4058 28.56 2.174475 2.173516
## 11245 38.02 1.282200 1.481106
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 4058 14.2 13.9 10.7 5.7
## 11245 23.7 5.1 21.2 49.9
## GSM9102 _nonUL mean _nonUL median _nonUL
## 4058 17.4 12.38 13.14
## 11245 38.3 27.64 25.67BRCA1 is highly expressed to approximately double the non-UL gene expression values. This could mean it is acting greatly on suppressing the tumor along with other network genes sending its production to an increase in the benign UL tumor.
Now lets look at this gene in the flu 1 day immunized samples if it is included in the data.
getMeanMedianFlu1('BRCA1')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.904542
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9097611## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 1153 3.565998 3.524617
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 1153 3.362609 3.484408 3.504512
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 1153 0.904542 0.9097611
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 1153 3.833138
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 1153 4.232549
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 1153 4.031393
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 1153 3.34295
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 1153 4.264876
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 1153 3.407837 3.852124
## median _healthyNonImmz
## 1153 3.852124BRCA1 is included in the flu 1 day immunized samples, and it is under expressed approximately 10% compared to healthy non-immunized samples.
How about BRCA1 in the flu 7 day immunized samples?
getMeanMedianFlu7('BRCA1')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.8333863
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.8365506## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 1153 3.292334 3.103902
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 1153 3.234686 3.210307 3.222497
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 1153 0.8333863 0.8365506
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 1153 3.833138
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 1153 4.232549
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 1153 4.031393
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 1153 3.34295
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 1153 4.264876
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 1153 3.407837 3.852124
## median _healthyNonImmz
## 1153 3.852124In the 7 day flu immunized samples the BRCA1 gene is underexpressed by almost 20%. That is interesting, hope there is no link to increased risk of breast cancer from flu shots.
The next gene is IL1B, an immunity gene:
serousSumms[5,3]## [1] "The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, Jul 2008]"It seems this interleukin antibody is a pain hypersensitivity gene for inflammation, likely responsible for inflammation and to prevent movement of strains, sprains, and other injuries immediately after they occur. Lets see the gene expression of this gene in UL then flu immunized samples.
IL1B in UL:
getMeanMedian('IL1B')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.6702186 0.7263643
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.6738895 0.8455804## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 4594 42.8 66.6 56.7 57.8 140.9 72.96
## 21932 41.6 57.4 42.0 36.7 11.3 37.80
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 4594 62.2 0.6702186 0.6738895
## 21932 39.7 0.7263643 0.8455804
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 4594 221.5 78.6 59.6 99.5
## 21932 128.8 50.2 6.9 43.7
## GSM9102 _nonUL mean _nonUL median _nonUL
## 4594 85.1 108.86 92.30
## 21932 30.6 52.04 46.95This gene IL1B is almost under expressed by 15-33% in UL compared to non-UL samples. Makes sense, as ULs aren’t painful but cause painful menstruations in some females.
IL1B in 1 day flu immunized samples:
getMeanMedianFlu1('IL1B')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 1.060949
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 1.108355## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 5098 6.664145 11.58816
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 5098 10.40672 9.553009 9.979867
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 5098 1.060949 1.108355
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5098 5.424972
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5098 5.598697
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5098 7.833018
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5098 12.81367
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5098 12.46592
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5098 9.889004 9.004213
## median _healthyNonImmz
## 5098 9.004213This gene is elevated 6-10 % more in flu immunized samples compared to non-immunized healthy samples after 1 day. This makes sense as it is early in the infection of an antigen and flu is normally associated with body aches and headaches.
IL1B in 7 day immunized flu samples.
getMeanMedianFlu7('IL1B')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 1.404076
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 1.40426## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 5098 12.89866 12.6459
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 5098 12.38324 12.6426 12.64425
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 5098 1.404076 1.40426
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5098 5.424972
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5098 5.598697
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5098 7.833018
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5098 12.81367
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5098 12.46592
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5098 9.889004 9.004213
## median _healthyNonImmz
## 5098 9.004213Wow! After 7 days, the pain hypersensitivity inflammatory interleukin, IL1B is elevated approximately 40% more in flu immunized samples after 7 days compared to non-immunized and healthy samples.
Our sixth gene related to serous fluid is PIK3CA:
serousSumms[6,3]## [1] "Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]"The gene cards gene summary for Entrez’ version says that PIK3CA is a cervical cancer associated oncogene. Lets see this gene expression in UL then flu immunized samples.
getMeanMedian('PIK3CA')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.6583226
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.6784124## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 3896 124.6 96.5 114.5 108.2 66.4 102.04
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 3896 105.12 0.6583226 0.6784124
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 3896 154.9 178.3 141.8 132.2 167.8
## mean _nonUL median _nonUL
## 3896 155 154.95Thats reassuring that, PIK3CA is expressed approximately 32-34% less in UL compared to non-UL samples as it is an oncogene that signals cervical cancer as the gene summary says.
PIK3CA in 1 day flu immunized samples:
getMeanMedianFlu1('PIK3CA')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9044685
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.8753614## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 7994 5.703198 5.370994
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 7994 5.8883 5.654164 5.678681
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 7994 0.9044685 0.8753614
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 7994 6.521786
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 7994 6.625757
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 7994 6.559634
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 7994 5.686797
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 7994 5.626983
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 7994 6.487241 6.251366
## median _healthyNonImmz
## 7994 6.487241In 1 day flu immunized samples PIK3CA is expressed 10-13% less than in healthy non-immunized samples.
PIK3CA in 7 day flu immunized samples:
getMeanMedianFlu7('PIK3CA')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.9072343
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.8828344## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 7994 5.782866 5.195146
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 7994 6.03635 5.671454 5.72716
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 7994 0.9072343 0.8828344
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 7994 6.521786
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 7994 6.625757
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 7994 6.559634
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 7994 5.686797
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 7994 5.626983
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 7994 6.487241 6.251366
## median _healthyNonImmz
## 7994 6.487241The cervical cancer gene is also 10-13% less expressed in 7 day flu immunized samples compared to healthy non-immunized.
The 7th gene is BRCA2:
serousSumms[7,3]## [1] "Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]"The above definition goes into the DNA replication of splicing on exons and the copy mutations of this gene that is an ovarian and breast cancer oncogene. It is a tumor suppressor gene like BRCA1. The Entrez gene summary above says BRCA2 where the exon 11 is a primary culprit in breast cancer for its gene host and recall that exons and introns both make up the DNA in replication but the introns are dropped. The amino acid build is of adenine 70 replicate motif in this specific exon. It is a mutation, because the wild type inherited is selected that causes breast cancer in its host instead of the mix of non breast cancer carrying genes in the host. That is my interpretation based on the summary. Tumors are an abundance of mutations that grow fast and in one location, cancerous or malignant if they spread and mutate other neighboring tissue, benign if they stay local and don’t spread.
So lets see how this BRCA2 gene expression fold change values are in the UL and flu immunized samples compared to their healthy counterparts.
getMeanMedian('BRCA2')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.9925926 0.8655022
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 2.336364 0.963000## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 7869 12.1 1.6 4.9 5.9 2.4 5.38
## 14103 2.6 33.5 17.8 26.5 18.7 19.82
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 7869 5.14 1.9925926 2.336364
## 14103 19.26 0.8655022 0.963000
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 7869 0.6 3.5 1.7 6.7
## 14103 26.7 39.5 14.5 17.1
## GSM9102 _nonUL mean _nonUL median _nonUL
## 7869 1.0 2.7 2.2
## 14103 16.7 22.9 20.0So, it looks like the BRCA2, a tumor suppressor, is working in a range of 14% under expressed to 133% over expressed in our UL samples compared to non-UL samples from the above output. There were two of these genes in the array data extracted, with no genotype information attached, but these genes do have different genotypes, hence there being two of these genes in the data. A lot of the genes in this data have more than one genotype the reason for the mean and median fold change values instead of just the fold change value on a one-to-one basis.
BRCA2 in the 1 day flu immunized samples:
getMeanMedianFlu1("BRCA2")## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.8976164
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.903051## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 1154 2.62758 2.43132
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 1154 2.729531 2.596144 2.611862
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 1154 0.8976164 0.903051
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 1154 3.11134
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 1154 3.295374
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 1154 3.144021
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 1154 2.578839
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 1154 2.748326
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 1154 2.475685 2.892264
## median _healthyNonImmz
## 1154 2.892264The BRCA2 gene is approximately 10% underexpressed in the 1 day flu immunized samples much like the BRCA1 gene was underexpressed the same approximate value.
BRCA2 in the 7 day flu immunized samples:
getMeanMedianFlu7('BRCA2')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.909866
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.913955## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 1154 2.687913 2.655226
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 1154 2.55158 2.631573 2.643399
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 1154 0.909866 0.913955
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 1154 3.11134
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 1154 3.295374
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 1154 3.144021
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 1154 2.578839
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 1154 2.748326
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 1154 2.475685 2.892264
## median _healthyNonImmz
## 1154 2.892264This gene, BRCA2, is also approximately 10% under expressed in 7 day flu immunized samples thats the same as the 1 day flu immunized and more than the BRCA1 7 day immunized samples that saw a decrease in gene expression of approximately 20%.
The 8th gene is anothe oncogene, KRAS:
serousSumms[8,3]## [1] "This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]"Lets see the fold change values of KRAS in UL and flu immunized samples.
KRAS in UL:
getMeanMedian('KRAS')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.426228 1.114362 1.651546
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.3569137 0.9407895 1.5224767## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 3536 192.3 437.8 452.9 325.7 304.2 342.58
## 3537 10.0 24.8 14.7 3.4 30.9 16.76
## 13731 123.5 407.9 230.2 158.7 201.1 224.28
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 3536 334.14 1.426228 1.3569137
## 3537 15.73 1.114362 0.9407895
## 13731 212.69 1.651546 1.5224767
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 3536 253.9 235.0 253.8 206.0
## 3537 18.4 2.3 23.0 19.1
## 13731 116.2 153.4 159.9 105.9
## GSM9102 _nonUL mean _nonUL median _nonUL
## 3536 252.3 240.20 246.25
## 3537 12.4 15.04 16.72
## 13731 143.6 135.80 139.70In UL samples the KRAS gene has a range of expression from 5% under to 65% over expressed, with most samples over expressed. That isn’t great news, but the Kirsten Ras gene is from the Kirsten Rat Sarcoma Virus studies that found the information on how this protein, KRAS, could turn on and off signaling pathways inside the nucleus for cell differentiation and proliferation. You can read more about this gene at https://en.wikipedia.org/wiki/KRAS.
Lets see how KRAS is expressed in flu immunized samples.
KRAS in 1 day flu immunized samples:
getMeanMedianFlu1('KRAS')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9075472
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9102692## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 5665 5.696294 5.800101
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 5665 5.800156 5.765517 5.782809
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 5665 0.9075472 0.9102692
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5665 6.92838
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5665 6.705617
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5665 6.931805
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5665 5.922192
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5665 5.718022
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5665 5.911121 6.352856
## median _healthyNonImmz
## 5665 6.352856KRAS is underexpressed approximately 10% in 1 day immunized flu samples compared to non-immunized and healthy samples.
KRAS in 7 day flu immunized samples:
getMeanMedianFlu7('KRAS')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.9547233
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.9535253## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 5665 6.125898 6.019764
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 5665 6.049998 6.06522 6.057609
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 5665 0.9547233 0.9535253
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5665 6.92838
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5665 6.705617
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5665 6.931805
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5665 5.922192
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5665 5.718022
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5665 5.911121 6.352856
## median _healthyNonImmz
## 5665 6.352856In 7 day immunized samples the KRAS oncogene is under expressed approximately 5%.
Lets discuss the KRAS gene some more. It is under expressed in immunized blood samples and over expressed up to 65% in UL tumor samples. It is one of the top ten genes returned searching genecards.org for genes associated with ‘serous fluid’ of the body cavities. The uterus is in the pericardium of the abdomen and pelvis with the other visceral organs. In rats, a mammal like humans obviously different, this KRAS gene is associated with pancreatic and colon cancer. This could be significant to study this gene in UL tissue, and as we all know when some networks slow or get backed up in the body, other diseases could occur. There are some comorbidities associated with UL, if a great number of women with ULs also get pancreatic or colon cancer. Otherwise, there is not. It does make this finding a possible gene target to watch out for in other cancer risks or health risks for females with ULs.
Lets move on to the 9th gene, IFNG:
serousSumms[9,3]## [1] "This gene encodes a soluble cytokine that is a member of the type II interferon class. The encoded protein is secreted by cells of both the innate and adaptive immune systems. The active protein is a homodimer that binds to the interferon gamma receptor which triggers a cellular response to viral and microbial infections. Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases. [provided by RefSeq, Dec 2015]"The gene IFNG is a cytokine, which is a pain inflammatory interleukin. The above description says those with a gene mutation in this gene will be prone to infections. This gene, IFNG, combats infections, so it makes sense that those with autoimmune disorders and mutations in this gene will be more at risk of viral and bacterial infections.
Lets see how IFNG is expressed in UL samples compared to non-UL samples.
getMeanMedian('IFNG')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.030266
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.076127## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 9832 15.9 31.1 49.4 27.7 42.7 33.36
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 9832 32.23 1.030266 1.076127
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 9832 50.2 27.5 29.2 24.3 30.7
## mean _nonUL median _nonUL
## 9832 32.38 29.95In the above data, we see that IFNG is over expressed by 5-10% in UL compared to non-UL samples, and that is good, since it fights infections in the body.
getMeanMedianFlu1('IFNG')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.8192229
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.8669836## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 5014 2.689282 3.978227
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 5014 4.1249 3.597469 3.787848
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 5014 0.8192229 0.8669836
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5014 4.368996
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5014 4.078136
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5014 4.808612
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5014 4.312713
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5014 4.101681
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5014 4.677779 4.39132
## median _healthyNonImmz
## 5014 4.368996IFNG is under expressed up to 20% in 1 day flu immunized samples. This makes sense as it is early in the stage of flu virus infection, even though the flu virus is deactivated it will be treated as an antigen.
getMeanMedianFlu7('IFNG')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 1.103063
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 1.100625## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 5014 4.773351 5.739567
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 5014 4.018791 4.843903 4.808627
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 5014 1.103063 1.100625
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5014 4.368996
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5014 4.078136
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5014 4.808612
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5014 4.312713
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5014 4.101681
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5014 4.677779 4.39132
## median _healthyNonImmz
## 5014 4.368996After 7 days of flu immunizations, the IFNG interleukin gene is increased approximately 10%, which also makes sense as this is the usual time period that symptoms show after infection as 1-2 weeks after infection from common knowledge on flu symptom internet searches that state such information. But https://www.healthline.com/health/how-long-does-the-flu-last says symptoms can show 1-4 days after infection. And the Center for Disease Control (CDC) says that the symptoms can show 1-7 days after becoming sick. Which could mean after being infected or after showing infection signs. More CDC information on this is available at: https://www.cdc.gov/flu/about/disease/spread.htm
“When Flu Spreads People with flu are most contagious in the first three to four days after their illness begins. Most healthy adults may be able to infect others beginning 1 day before symptoms develop and up to 5 to 7 days after becoming sick. Children and some people with weakened immune systems may pass the virus for longer than 7 days.”-CDC
Our 10th serous fluid gene is ERBB2:
serousSumms[10,3]## [1] "This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]"ERBB2 seems to be another oncogene that indicated increased expression in breast and ovarian tumors. It encodes a member of the epidermal growth factor receptor family. The epidermis is the skin and mucous linings of the body’s organs. Lets see how this gene is expressed in ULs and flu immunized samples.
ERBB2 in UL:
getMeanMedian('ERBB2')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.4688547 0.8466579
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.3979181 0.7805664## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 10377 33.3 6.5 16.2 9.7 4.3 14.00
## 16206 163.9 151.9 117.6 182.1 159.7 155.04
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 10377 11.85 0.4688547 0.3979181
## 16206 157.37 0.8466579 0.7805664
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 10377 31.6 29.7 31.5 28.4
## 16206 78.2 249.2 220.1 230.1
## GSM9102 _nonUL mean _nonUL median _nonUL
## 10377 28.1 29.86 29.78
## 16206 138.0 183.12 201.61The results for ERBB2 in UL tissue are that this gene is approximately 15-60% under expressed in UL compared to non-UL samples. That is reassuring as the Entrez gene summary for ERBB2 stated that over expression of ERBB2 is associated with ovarian and breast tumors as well as cancer.
Now lets see how ERBB2 does in 1 day flu immunized samples:
getMeanMedianFlu1('ERBB2')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.8570737
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.8927011## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 3318 2.773421 2.567352
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 3318 2.837194 2.725989 2.749705
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 3318 0.8570737 0.8927011
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 3318 3.536601
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 3318 3.574591
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 3318 3.080208
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 3318 3.00346
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 3318 2.980136
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 3318 2.908465 3.180577
## median _healthyNonImmz
## 3318 3.080208ERBB2 is also under expressed in the 1 day flu immunized samples by approximately 10-15%.
ERBB2 gene in 7 day flu immunized samples:
getMeanMedianFlu7('ERBB2')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.8448535
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.8761868## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 3318 2.710553 2.615356
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 3318 2.735456 2.687122 2.698837
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 3318 0.8448535 0.8761868
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 3318 3.536601
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 3318 3.574591
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 3318 3.080208
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 3318 3.00346
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 3318 2.980136
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 3318 2.908465 3.180577
## median _healthyNonImmz
## 3318 3.080208ERBB2 is under expressed after 7 days of being immunized with the flu compared to healthy and non-immunized samples. The fold change values are 12-16% less after 7 days of immunizations.
We have seen that some of these 10 genes in UL and flu samples are over expressed or under expressed more than 10%. Lets recall those genes dramatically over and under expressed in the UL samples, then the flu samples. - UL: - over expressed genes more than 10%: - TP53 - BRCA1 - BRCA2 - IFNG - KRAS - under expressed genes by more than 10%: - IL1B - PIK3CA - ERBB2 - 1 day flu: - over expressed by more than 10%: - TNF - under expressed by more than 10%: - IL10 - BRCA1 - IL1B - PIK3CA - BRCA2 - KRAS - IFNG - ERBB2 - 7 day flu: - over expressed by more than 10%: - TNF - IL1B - under expressed by more than 10%: - BRCA1 - PIK3CA - ERBB2
Lets make a list of these 25 serous fluid genes and get the fold change values for all of these genes in the UL, 1 day, and 3 day flu immunization data frames.
serousList <- serousSumms$gene
serousList## [1] "TP53" "TNF" "IL10" "BRCA1" "IL1B" "PIK3CA" "BRCA2" "KRAS"
## [9] "IFNG" "ERBB2" "PTEN" "IL6" "CCL2" "AKT1" "CTNNB1" "BRAF"
## [17] "MUC1" "CDH1" "APOE" "HRAS" "VEGFA" "CFH" "NRAS" "AFP"
## [25] "CXCL8"UL$first <- as.character(UL$first)
UL_serous <- subset(UL, UL$first %in% serousList )
UL_serous <- UL_serous[,c(2:7)]
colnames(UL_serous)[6] <- 'gene'
UL_serous <- UL_serous[!duplicated(UL_serous),]
row.names(UL_serous) <- NULL
UL_serous## GSM9093 GSM9094 GSM9095 GSM9096 GSM9097 gene
## 1 25.3 14.4 33.2 16.0 4.2 CDH1
## 2 1.9 2.1 2.3 9.2 2.1 CDH1
## 3 1022.8 1591.3 1054.3 877.1 539.5 CTNNB1
## 4 161.6 182.3 113.8 151.1 142.1 TP53
## 5 109.4 54.8 39.4 43.7 56.6 NRAS
## 6 10.6 38.8 26.4 31.1 19.8 CXCL8
## 7 475.6 46.0 47.5 146.5 189.2 APOE
## 8 291.2 61.3 54.2 181.5 248.0 APOE
## 9 192.3 437.8 452.9 325.7 304.2 KRAS
## 10 10.0 24.8 14.7 3.4 30.9 KRAS
## 11 318.1 164.7 196.4 255.8 257.5 PTEN
## 12 49.9 52.4 71.3 45.2 50.0 PTEN
## 13 124.6 96.5 114.5 108.2 66.4 PIK3CA
## 14 6.8 38.7 26.7 30.2 32.2 BRCA1
## 15 16.0 31.5 18.8 17.4 42.3 AFP
## 16 42.8 66.6 56.7 57.8 140.9 IL1B
## 17 29.1 35.8 46.5 43.5 61.1 IL6
## 18 25.1 74.5 27.4 63.9 41.4 BRAF
## 19 43.4 35.9 42.7 33.4 49.0 TNF
## 20 251.2 160.4 192.7 235.2 193.9 AKT1
## 21 40.8 4.7 27.4 16.2 36.1 IL10
## 22 52.3 74.9 68.0 64.3 73.4 MUC1
## 23 12.1 1.6 4.9 5.9 2.4 BRCA2
## 24 15.9 31.1 49.4 27.7 42.7 IFNG
## 25 563.2 320.8 597.0 513.9 374.6 VEGFA
## 26 295.5 109.4 115.7 148.5 91.5 VEGFA
## 27 33.3 6.5 16.2 9.7 4.3 ERBB2
## 28 67.0 59.5 43.6 35.8 18.4 TP53
## 29 1.3 3.6 2.9 2.8 2.2 CXCL8
## 30 237.2 102.0 138.7 124.3 43.8 VEGFA
## 31 34.1 51.8 35.3 29.7 34.1 MUC1
## 32 89.4 65.3 89.0 124.5 104.3 PTEN
## 33 22.4 23.4 40.6 45.7 45.1 BRCA1
## 34 593.7 270.8 403.4 374.2 168.6 VEGFA
## 35 461.4 136.8 122.2 211.2 265.3 APOE
## 36 195.5 88.6 136.1 107.3 140.4 HRAS
## 37 21.8 16.6 44.5 6.4 19.8 MUC1
## 38 76.8 69.0 121.1 58.3 51.3 CFH
## 39 123.5 407.9 230.2 158.7 201.1 KRAS
## 40 2.6 33.5 17.8 26.5 18.7 BRCA2
## 41 62.8 46.7 44.0 36.5 26.7 CFH
## 42 98.2 51.5 87.3 7.5 7.8 CCL2
## 43 163.9 151.9 117.6 182.1 159.7 ERBB2
## 44 199.3 143.1 121.8 178.0 132.9 PTEN
## 45 41.6 57.4 42.0 36.7 11.3 IL1BnonUL$first <- as.character(nonUL$first)
nonUL_serous <- subset(nonUL, nonUL$first %in% serousList )
nonUL_serous <- nonUL_serous[,c(2:7)]
colnames(nonUL_serous)[6] <- 'gene'
nonUL_serous <- nonUL_serous[!duplicated(nonUL_serous),]
row.names(nonUL_serous) <- NULL
nonUL_serous## GSM9098 GSM9099 GSM9100 GSM9101 GSM9102 gene
## 1 24.9 16.1 3.9 19.2 7.6 CDH1
## 2 15.5 203.2 11.3 52.4 3.2 CDH1
## 3 1140.2 530.5 993.0 537.4 457.3 CTNNB1
## 4 120.3 70.0 103.8 117.5 117.6 TP53
## 5 74.4 107.0 65.9 59.0 62.5 NRAS
## 6 537.8 46.9 17.1 24.0 18.3 CXCL8
## 7 136.4 190.3 287.9 109.1 215.6 APOE
## 8 163.6 122.1 213.3 93.4 142.9 APOE
## 9 253.9 235.0 253.8 206.0 252.3 KRAS
## 10 18.4 2.3 23.0 19.1 12.4 KRAS
## 11 219.6 204.6 224.0 201.1 256.3 PTEN
## 12 48.4 62.2 53.0 46.3 55.3 PTEN
## 13 154.9 178.3 141.8 132.2 167.8 PIK3CA
## 14 14.2 13.9 10.7 5.7 17.4 BRCA1
## 15 25.6 2.9 19.9 8.2 15.3 AFP
## 16 221.5 78.6 59.6 99.5 85.1 IL1B
## 17 617.6 72.1 76.6 43.5 103.3 IL6
## 18 62.8 26.2 50.9 44.0 31.3 BRAF
## 19 47.2 41.7 28.0 61.5 26.8 TNF
## 20 146.0 145.0 230.0 201.0 192.7 AKT1
## 21 37.1 27.7 25.8 10.9 37.6 IL10
## 22 64.6 263.7 105.5 107.8 97.6 MUC1
## 23 0.6 3.5 1.7 6.7 1.0 BRCA2
## 24 50.2 27.5 29.2 24.3 30.7 IFNG
## 25 1045.4 1067.3 962.7 1197.7 1231.8 VEGFA
## 26 417.1 490.5 576.3 470.4 408.2 VEGFA
## 27 31.6 29.7 31.5 28.4 28.1 ERBB2
## 28 63.2 27.3 53.7 36.9 31.6 TP53
## 29 100.9 10.5 2.6 10.4 2.2 CXCL8
## 30 307.5 448.9 451.0 296.1 273.1 VEGFA
## 31 42.1 101.6 44.8 66.8 42.7 MUC1
## 32 121.4 44.6 71.8 106.1 109.0 PTEN
## 33 23.7 5.1 21.2 49.9 38.3 BRCA1
## 34 785.4 870.0 859.1 843.2 718.2 VEGFA
## 35 188.7 242.6 331.5 194.3 197.4 APOE
## 36 99.8 123.7 117.3 142.9 133.2 HRAS
## 37 25.8 234.5 87.1 83.1 102.7 MUC1
## 38 132.1 69.6 125.5 149.0 207.2 CFH
## 39 116.2 153.4 159.9 105.9 143.6 KRAS
## 40 26.7 39.5 14.5 17.1 16.7 BRCA2
## 41 49.1 21.4 54.6 113.4 118.8 CFH
## 42 530.4 720.5 346.3 51.9 132.4 CCL2
## 43 78.2 249.2 220.1 230.1 138.0 ERBB2
## 44 175.7 144.8 154.2 209.7 229.6 PTEN
## 45 128.8 50.2 6.9 43.7 30.6 IL1BLets add the mean fold change for each gene to each table.
UL_serous2 <- UL_serous %>% group_by(gene) %>% summarise_at(vars('GSM9093':'GSM9097'), mean)
names <- UL_serous2$gene
UL_serous3 <- UL_serous2[,c(2:6)]
UL_serous3$mean <- apply(UL_serous3,1,mean)
colnames(UL_serous3) <- paste('UL_',colnames(UL_serous3), sep='')
UL_serous4 <- as.data.frame(UL_serous3)
row.names(UL_serous4) <- names
UL_serous4## UL_GSM9093 UL_GSM9094 UL_GSM9095 UL_GSM9096 UL_GSM9097 UL_mean
## AFP 16.00000 31.50000 18.80000 17.40000 42.30000 25.200
## AKT1 251.20000 160.40000 192.70000 235.20000 193.90000 206.680
## APOE 409.40000 81.36667 74.63333 179.73333 234.16667 195.860
## BRAF 25.10000 74.50000 27.40000 63.90000 41.40000 46.460
## BRCA1 14.60000 31.05000 33.65000 37.95000 38.65000 31.180
## BRCA2 7.35000 17.55000 11.35000 16.20000 10.55000 12.600
## CCL2 98.20000 51.50000 87.30000 7.50000 7.80000 50.460
## CDH1 13.60000 8.25000 17.75000 12.60000 3.15000 11.070
## CFH 69.80000 57.85000 82.55000 47.40000 39.00000 59.320
## CTNNB1 1022.80000 1591.30000 1054.30000 877.10000 539.50000 1017.000
## CXCL8 5.95000 21.20000 14.65000 16.95000 11.00000 13.950
## ERBB2 98.60000 79.20000 66.90000 95.90000 82.00000 84.520
## HRAS 195.50000 88.60000 136.10000 107.30000 140.40000 133.580
## IFNG 15.90000 31.10000 49.40000 27.70000 42.70000 33.360
## IL10 40.80000 4.70000 27.40000 16.20000 36.10000 25.040
## IL1B 42.20000 62.00000 49.35000 47.25000 76.10000 55.380
## IL6 29.10000 35.80000 46.50000 43.50000 61.10000 43.200
## KRAS 108.60000 290.16667 232.60000 162.60000 178.73333 194.540
## MUC1 36.06667 47.76667 49.26667 33.46667 42.43333 41.800
## NRAS 109.40000 54.80000 39.40000 43.70000 56.60000 60.780
## PIK3CA 124.60000 96.50000 114.50000 108.20000 66.40000 102.040
## PTEN 164.17500 106.37500 119.62500 150.87500 136.17500 135.445
## TNF 43.40000 35.90000 42.70000 33.40000 49.00000 40.880
## TP53 114.30000 120.90000 78.70000 93.45000 80.25000 97.520
## VEGFA 422.40000 200.75000 313.70000 290.22500 169.62500 279.340nonUL_serous2 <- nonUL_serous %>% group_by(gene) %>% summarise_at(vars('GSM9098':'GSM9102'), mean)
names <- nonUL_serous2$gene
nonUL_serous3 <- nonUL_serous2[,c(2:6)]
nonUL_serous3$mean <- apply(nonUL_serous3,1,mean)
colnames(nonUL_serous3) <- paste('nonUL_',colnames(nonUL_serous3), sep='')
nonUL_serous4 <- as.data.frame(nonUL_serous3)
row.names(nonUL_serous4) <- names
nonUL_serous4## nonUL_GSM9098 nonUL_GSM9099 nonUL_GSM9100 nonUL_GSM9101 nonUL_GSM9102
## AFP 25.60000 2.9000 19.90000 8.2000 15.300
## AKT1 146.00000 145.0000 230.00000 201.0000 192.700
## APOE 162.90000 185.0000 277.56667 132.2667 185.300
## BRAF 62.80000 26.2000 50.90000 44.0000 31.300
## BRCA1 18.95000 9.5000 15.95000 27.8000 27.850
## BRCA2 13.65000 21.5000 8.10000 11.9000 8.850
## CCL2 530.40000 720.5000 346.30000 51.9000 132.400
## CDH1 20.20000 109.6500 7.60000 35.8000 5.400
## CFH 90.60000 45.5000 90.05000 131.2000 163.000
## CTNNB1 1140.20000 530.5000 993.00000 537.4000 457.300
## CXCL8 319.35000 28.7000 9.85000 17.2000 10.250
## ERBB2 54.90000 139.4500 125.80000 129.2500 83.050
## HRAS 99.80000 123.7000 117.30000 142.9000 133.200
## IFNG 50.20000 27.5000 29.20000 24.3000 30.700
## IL10 37.10000 27.7000 25.80000 10.9000 37.600
## IL1B 175.15000 64.4000 33.25000 71.6000 57.850
## IL6 617.60000 72.1000 76.60000 43.5000 103.300
## KRAS 129.50000 130.2333 145.56667 110.3333 136.100
## MUC1 44.16667 199.9333 79.13333 85.9000 81.000
## NRAS 74.40000 107.0000 65.90000 59.0000 62.500
## PIK3CA 154.90000 178.3000 141.80000 132.2000 167.800
## PTEN 141.27500 114.0500 125.75000 140.8000 162.550
## TNF 47.20000 41.7000 28.00000 61.5000 26.800
## TP53 91.75000 48.6500 78.75000 77.2000 74.600
## VEGFA 638.85000 719.1750 712.27500 701.8500 657.825
## nonUL_mean
## AFP 14.38000
## AKT1 182.94000
## APOE 188.60667
## BRAF 43.04000
## BRCA1 20.01000
## BRCA2 12.80000
## CCL2 356.30000
## CDH1 35.73000
## CFH 104.07000
## CTNNB1 731.68000
## CXCL8 77.07000
## ERBB2 106.49000
## HRAS 123.38000
## IFNG 32.38000
## IL10 27.82000
## IL1B 80.45000
## IL6 182.62000
## KRAS 130.34667
## MUC1 98.02667
## NRAS 73.76000
## PIK3CA 155.00000
## PTEN 136.88500
## TNF 41.04000
## TP53 74.19000
## VEGFA 685.99500UL_df <- cbind(UL_serous4, nonUL_serous4)
UL_df <- UL_df[,c(1:5,7:11,6,12)]
UL_df$UL_foldChange <- UL_df$UL_mean/UL_df$nonUL_mean
UL_df## UL_GSM9093 UL_GSM9094 UL_GSM9095 UL_GSM9096 UL_GSM9097 nonUL_GSM9098
## AFP 16.00000 31.50000 18.80000 17.40000 42.30000 25.60000
## AKT1 251.20000 160.40000 192.70000 235.20000 193.90000 146.00000
## APOE 409.40000 81.36667 74.63333 179.73333 234.16667 162.90000
## BRAF 25.10000 74.50000 27.40000 63.90000 41.40000 62.80000
## BRCA1 14.60000 31.05000 33.65000 37.95000 38.65000 18.95000
## BRCA2 7.35000 17.55000 11.35000 16.20000 10.55000 13.65000
## CCL2 98.20000 51.50000 87.30000 7.50000 7.80000 530.40000
## CDH1 13.60000 8.25000 17.75000 12.60000 3.15000 20.20000
## CFH 69.80000 57.85000 82.55000 47.40000 39.00000 90.60000
## CTNNB1 1022.80000 1591.30000 1054.30000 877.10000 539.50000 1140.20000
## CXCL8 5.95000 21.20000 14.65000 16.95000 11.00000 319.35000
## ERBB2 98.60000 79.20000 66.90000 95.90000 82.00000 54.90000
## HRAS 195.50000 88.60000 136.10000 107.30000 140.40000 99.80000
## IFNG 15.90000 31.10000 49.40000 27.70000 42.70000 50.20000
## IL10 40.80000 4.70000 27.40000 16.20000 36.10000 37.10000
## IL1B 42.20000 62.00000 49.35000 47.25000 76.10000 175.15000
## IL6 29.10000 35.80000 46.50000 43.50000 61.10000 617.60000
## KRAS 108.60000 290.16667 232.60000 162.60000 178.73333 129.50000
## MUC1 36.06667 47.76667 49.26667 33.46667 42.43333 44.16667
## NRAS 109.40000 54.80000 39.40000 43.70000 56.60000 74.40000
## PIK3CA 124.60000 96.50000 114.50000 108.20000 66.40000 154.90000
## PTEN 164.17500 106.37500 119.62500 150.87500 136.17500 141.27500
## TNF 43.40000 35.90000 42.70000 33.40000 49.00000 47.20000
## TP53 114.30000 120.90000 78.70000 93.45000 80.25000 91.75000
## VEGFA 422.40000 200.75000 313.70000 290.22500 169.62500 638.85000
## nonUL_GSM9099 nonUL_GSM9100 nonUL_GSM9101 nonUL_GSM9102 UL_mean
## AFP 2.9000 19.90000 8.2000 15.300 25.200
## AKT1 145.0000 230.00000 201.0000 192.700 206.680
## APOE 185.0000 277.56667 132.2667 185.300 195.860
## BRAF 26.2000 50.90000 44.0000 31.300 46.460
## BRCA1 9.5000 15.95000 27.8000 27.850 31.180
## BRCA2 21.5000 8.10000 11.9000 8.850 12.600
## CCL2 720.5000 346.30000 51.9000 132.400 50.460
## CDH1 109.6500 7.60000 35.8000 5.400 11.070
## CFH 45.5000 90.05000 131.2000 163.000 59.320
## CTNNB1 530.5000 993.00000 537.4000 457.300 1017.000
## CXCL8 28.7000 9.85000 17.2000 10.250 13.950
## ERBB2 139.4500 125.80000 129.2500 83.050 84.520
## HRAS 123.7000 117.30000 142.9000 133.200 133.580
## IFNG 27.5000 29.20000 24.3000 30.700 33.360
## IL10 27.7000 25.80000 10.9000 37.600 25.040
## IL1B 64.4000 33.25000 71.6000 57.850 55.380
## IL6 72.1000 76.60000 43.5000 103.300 43.200
## KRAS 130.2333 145.56667 110.3333 136.100 194.540
## MUC1 199.9333 79.13333 85.9000 81.000 41.800
## NRAS 107.0000 65.90000 59.0000 62.500 60.780
## PIK3CA 178.3000 141.80000 132.2000 167.800 102.040
## PTEN 114.0500 125.75000 140.8000 162.550 135.445
## TNF 41.7000 28.00000 61.5000 26.800 40.880
## TP53 48.6500 78.75000 77.2000 74.600 97.520
## VEGFA 719.1750 712.27500 701.8500 657.825 279.340
## nonUL_mean UL_foldChange
## AFP 14.38000 1.7524339
## AKT1 182.94000 1.1297693
## APOE 188.60667 1.0384575
## BRAF 43.04000 1.0794610
## BRCA1 20.01000 1.5582209
## BRCA2 12.80000 0.9843750
## CCL2 356.30000 0.1416222
## CDH1 35.73000 0.3098237
## CFH 104.07000 0.5700010
## CTNNB1 731.68000 1.3899519
## CXCL8 77.07000 0.1810043
## ERBB2 106.49000 0.7936895
## HRAS 123.38000 1.0826714
## IFNG 32.38000 1.0302656
## IL10 27.82000 0.9000719
## IL1B 80.45000 0.6883779
## IL6 182.62000 0.2365568
## KRAS 130.34667 1.4924816
## MUC1 98.02667 0.4264146
## NRAS 73.76000 0.8240239
## PIK3CA 155.00000 0.6583226
## PTEN 136.88500 0.9894802
## TNF 41.04000 0.9961014
## TP53 74.19000 1.3144629
## VEGFA 685.99500 0.4072041Lets combine the gene summaries to our UL data.
UL_df$gene <- row.names(UL_df)
ULDF <- merge(serousSumms,UL_df, by.x='gene', by.y='gene')
ULDF## gene proteinSearched
## 1 AFP serous-fluid
## 2 AKT1 serous-fluid
## 3 APOE serous-fluid
## 4 BRAF serous-fluid
## 5 BRCA1 serous-fluid
## 6 BRCA2 serous-fluid
## 7 CCL2 serous-fluid
## 8 CDH1 serous-fluid
## 9 CFH serous-fluid
## 10 CTNNB1 serous-fluid
## 11 CXCL8 serous-fluid
## 12 ERBB2 serous-fluid
## 13 HRAS serous-fluid
## 14 IFNG serous-fluid
## 15 IL10 serous-fluid
## 16 IL1B serous-fluid
## 17 IL6 serous-fluid
## 18 KRAS serous-fluid
## 19 MUC1 serous-fluid
## 20 NRAS serous-fluid
## 21 PIK3CA serous-fluid
## 22 PTEN serous-fluid
## 23 TNF serous-fluid
## 24 TP53 serous-fluid
## 25 VEGFA serous-fluid
## EntrezSummary
## 1 This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing advanced gastric cancer. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. [provided by RefSeq, Oct 2019]
## 2 The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]
## 3 The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]
## 4 This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]
## 5 This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]
## 6 Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]
## 7 This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. [provided by RefSeq, Jul 2013]
## 8 This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]
## 9 This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]
## 10 The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
## 11 The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is commonly referred to as interleukin-8 (IL-8). IL-8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection. Bacterial and viral products rapidly induce IL-8 expression. IL-8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). This gene is believed to play a role in the pathogenesis of the lower respiratory tract infection bronchiolitis, a common respiratory tract disease caused by the respiratory syncytial virus (RSV). The overproduction of this proinflammatory protein is thought to cause the lung inflammation associated with csytic fibrosis. This proinflammatory protein is also suspected of playing a role in coronary artery disease and endothelial dysfunction. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor. The binding of IL-8 to one of its receptors (IL-8RB/CXCR2) increases the permeability of blood vessels and increasing levels of IL-8 are positively correlated with increased severity of multiple disease outcomes (eg, sepsis). This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, May 2020]
## 12 This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]
## 13 This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]
## 14 This gene encodes a soluble cytokine that is a member of the type II interferon class. The encoded protein is secreted by cells of both the innate and adaptive immune systems. The active protein is a homodimer that binds to the interferon gamma receptor which triggers a cellular response to viral and microbial infections. Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases. [provided by RefSeq, Dec 2015]
## 15 The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. [provided by RefSeq, May 2020]
## 16 The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, Jul 2008]
## 17 This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
## 18 This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
## 19 This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]
## 20 This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011]
## 21 Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]
## 22 This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
## 23 This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]
## 24 This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]
## 25 This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation. This gene is upregulated in many known tumors and its expression is correlated with tumor stage and progression. Elevated levels of this protein are found in patients with POEMS syndrome, also known as Crow-Fukase syndrome. Allelic variants of this gene have been associated with microvascular complications of diabetes 1 (MVCD1) and atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been described. There is also evidence for alternative translation initiation from upstream non-AUG (CUG) codons resulting in additional isoforms. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is antiangiogenic. Expression of some isoforms derived from the AUG start codon is regulated by a small upstream open reading frame, which is located within an internal ribosome entry site. The VEGF levels are increased in SARS-CoV-2 infection, thus promoting inflammation by increasing the level of angiopoietin II (Ang II), one of the two products of the SARS-CoV-2-attacking target, angiotensin-converting enzyme 2 (ACE2). In turn, Ang II facilitates the elevation of VEGF, forming a vicious cycle in the release of inflammatory cytokines. [provided by RefSeq, Jun 2020]
## GeneCardsSummary
## 1 AFP (Alpha Fetoprotein) is a Protein Coding gene. Diseases associated with AFP include Alpha-Fetoprotein Deficiency and Alpha-Fetoprotein, Hereditary Persistence Of. Among its related pathways are FOXA2 and FOXA3 transcription factor networks and Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers. An important paralog of this gene is ALB.
## 2 AKT1 (AKT Serine/Threonine Kinase 1) is a Protein Coding gene. Diseases associated with AKT1 include Proteus Syndrome and Cowden Syndrome 6. Among its related pathways are Regulation of TP53 Activity through Acetylation and Association Between Physico-Chemical Features and Toxicity Associated Pathways. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is AKT3.
## 3 APOE (Apolipoprotein E) is a Protein Coding gene. Diseases associated with APOE include Lipoprotein Glomerulopathy and Hyperlipoproteinemia, Type Iii. Among its related pathways are Neuroscience and Lipoprotein metabolism. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and signaling receptor binding. An important paralog of this gene is APOA4.
## 4 BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with BRAF include Cardiofaciocutaneous Syndrome 1 and Lung Cancer. Among its related pathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and Negative regulation of MAPK pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is RAF1.
## 5 BRCA1 (BRCA1 DNA Repair Associated) is a Protein Coding gene. Diseases associated with BRCA1 include Breast-Ovarian Cancer, Familial 1 and Fanconi Anemia, Complementation Group S. Among its related pathways are ATM Pathway and Homologous DNA Pairing and Strand Exchange. Gene Ontology (GO) annotations related to this gene include RNA binding and ligase activity.
## 6 BRCA2 (BRCA2 DNA Repair Associated) is a Protein Coding gene. Diseases associated with BRCA2 include Fanconi Anemia, Complementation Group D1 and Breast Cancer. Among its related pathways are Homologous DNA Pairing and Strand Exchange and Meiosis. Gene Ontology (GO) annotations related to this gene include protease binding and histone acetyltransferase activity.
## 7 CCL2 (C-C Motif Chemokine Ligand 2) is a Protein Coding gene. Diseases associated with CCL2 include Neural Tube Defects and Human Immunodeficiency Virus Type 1. Among its related pathways are G-protein signaling Ras family GTPases in kinase cascades (scheme) and Folate Metabolism. Gene Ontology (GO) annotations related to this gene include protein kinase activity and heparin binding. An important paralog of this gene is CCL7.
## 8 CDH1 (Cadherin 1) is a Protein Coding gene. Diseases associated with CDH1 include Blepharocheilodontic Syndrome 1 and Gastric Cancer, Hereditary Diffuse. Among its related pathways are Regulation of Wnt-mediated beta catenin signaling and target gene transcription and Preimplantation Embryo. Gene Ontology (GO) annotations related to this gene include calcium ion binding and protein phosphatase binding. An important paralog of this gene is CDH3.
## 9 CFH (Complement Factor H) is a Protein Coding gene. Diseases associated with CFH include Complement Factor H Deficiency and Hemolytic Uremic Syndrome, Atypical 1. Among its related pathways are Innate Immune System and Complement and coagulation cascades. Gene Ontology (GO) annotations related to this gene include heparin binding and heparan sulfate proteoglycan binding. An important paralog of this gene is CFHR5.
## 10 CTNNB1 (Catenin Beta 1) is a Protein Coding gene. Diseases associated with CTNNB1 include Pilomatrixoma and Neurodevelopmental Disorder With Spastic Diplegia And Visual Defects. Among its related pathways are Association Between Physico-Chemical Features and Toxicity Associated Pathways and Regulation of Wnt-mediated beta catenin signaling and target gene transcription. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and binding. An important paralog of this gene is JUP.
## 11 CXCL8 (C-X-C Motif Chemokine Ligand 8) is a Protein Coding gene. Diseases associated with CXCL8 include Melanoma and Adult Respiratory Distress Syndrome. Among its related pathways are Regulation of Wnt-mediated beta catenin signaling and target gene transcription and Transcriptional misregulation in cancer. Gene Ontology (GO) annotations related to this gene include chemokine activity and interleukin-8 receptor binding. An important paralog of this gene is PPBP.
## 12 ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2) is a Protein Coding gene. Diseases associated with ERBB2 include Glioma Susceptibility 1 and Gastric Cancer. Among its related pathways are Association Between Physico-Chemical Features and Toxicity Associated Pathways and RET signaling. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is EGFR.
## 13 HRAS (HRas Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with HRAS include Costello Syndrome and Schimmelpenning-Feuerstein-Mims Syndrome. Among its related pathways are Negative regulation of MAPK pathway and GDNF-Family Ligands and Receptor Interactions. Gene Ontology (GO) annotations related to this gene include GTP binding and protein C-terminus binding. An important paralog of this gene is KRAS.
## 14 IFNG (Interferon Gamma) is a Protein Coding gene. Diseases associated with IFNG include Hepatitis C Virus and Tuberous Sclerosis 2. Among its related pathways are Folate Metabolism and Tuberculosis. Gene Ontology (GO) annotations related to this gene include cytokine activity and interferon-gamma receptor binding.
## 15 IL10 (Interleukin 10) is a Protein Coding gene. Diseases associated with IL10 include Graft-Versus-Host Disease and Human Immunodeficiency Virus Type 1. Among its related pathways are Tuberculosis and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include cytokine activity and interleukin-10 receptor binding. An important paralog of this gene is IL20.
## 16 IL1B (Interleukin 1 Beta) is a Protein Coding gene. Diseases associated with IL1B include Gastric Cancer, Hereditary Diffuse and Toxic Shock Syndrome. Among its related pathways are Monoamine Transport and Bacterial infections in CF airways. Gene Ontology (GO) annotations related to this gene include protein domain specific binding and interleukin-1 receptor binding. An important paralog of this gene is IL36RN.
## 17 IL6 (Interleukin 6) is a Protein Coding gene. Diseases associated with IL6 include Kaposi Sarcoma and Rheumatoid Arthritis, Systemic Juvenile. Among its related pathways are Transcriptional misregulation in cancer and Folate Metabolism. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and growth factor activity.
## 18 KRAS (KRAS Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with KRAS include Oculoectodermal Syndrome and Noonan Syndrome 3. Among its related pathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and Negative regulation of MAPK pathway. Gene Ontology (GO) annotations related to this gene include GTP binding. An important paralog of this gene is NRAS.
## 19 MUC1 (Mucin 1, Cell Surface Associated) is a Protein Coding gene. Diseases associated with MUC1 include Medullary Cystic Kidney Disease 1 and Syringoma. Among its related pathways are Defective C1GALT1C1 causes Tn polyagglutination syndrome (TNPS) and Cell adhesion_Cell-matrix glycoconjugates. Gene Ontology (GO) annotations related to this gene include RNA polymerase II proximal promoter sequence-specific DNA binding and p53 binding.
## 20 NRAS (NRAS Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with NRAS include Ras-Associated Autoimmune Leukoproliferative Disorder and Melanocytic Nevus Syndrome, Congenital. Among its related pathways are Negative regulation of MAPK pathway and NGF Pathway. Gene Ontology (GO) annotations related to this gene include GTP binding. An important paralog of this gene is KRAS.
## 21 PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) is a Protein Coding gene. Diseases associated with PIK3CA include Hepatocellular Carcinoma and Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome. Among its related pathways are GDNF-Family Ligands and Receptor Interactions and RET signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein serine/threonine kinase activity. An important paralog of this gene is PIK3CB.
## 22 PTEN (Phosphatase And Tensin Homolog) is a Protein Coding gene. Diseases associated with PTEN include Cowden Syndrome 1 and Macrocephaly/Autism Syndrome. Among its related pathways are RET signaling and B cell receptor signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include protein kinase binding and magnesium ion binding. An important paralog of this gene is TPTE2.
## 23 TNF (Tumor Necrosis Factor) is a Protein Coding gene. Diseases associated with TNF include Asthma and Malaria. Among its related pathways are Apoptosis Modulation and Signaling and Monoamine Transport. Gene Ontology (GO) annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is LTB.
## 24 TP53 (Tumor Protein P53) is a Protein Coding gene. Diseases associated with TP53 include Li-Fraumeni Syndrome and Osteogenic Sarcoma. Among its related pathways are Apoptosis Modulation and Signaling and Regulation of TP53 Activity through Acetylation. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is TP63.
## 25 VEGFA (Vascular Endothelial Growth Factor A) is a Protein Coding gene. Diseases associated with VEGFA include Microvascular Complications Of Diabetes 1 and Poems Syndrome. Among its related pathways are HIF1Alpha Pathway and Cell adhesion_Plasmin signaling. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein heterodimerization activity. An important paralog of this gene is PGF.
## UniProtKB_Summary
## 1 Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties.\n FETA_HUMAN,P02771\n
## 2 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174, PubMed:20231902). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768).\n AKT1_HUMAN,P31749\n
## 3 APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:6860692, PubMed:1911868, PubMed:14754908). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:6860692, PubMed:2762297, PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908, PubMed:23620513). Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:6860692, PubMed:2762297, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:6860692, PubMed:1911868). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:2762297, PubMed:1917954, PubMed:7768901, PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194, PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945). Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:9395455, PubMed:9488694, PubMed:23676495, PubMed:7635945). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:23676495, PubMed:29516132). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues (PubMed:2762297, PubMed:29516132). By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:2762297, PubMed:1917954, PubMed:29516132). APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis (PubMed:9395455, PubMed:14754908, PubMed:23620513). First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513). Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes (PubMed:9395455). APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting (PubMed:8939961, PubMed:25173806). APOE in also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). APOE, may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP (PubMed:28111074).\n APOE_HUMAN,P02649\n
## 4 Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179).\n BRAF_HUMAN,P15056\n
## 5 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator (PubMed:20160719).\n BRCA1_HUMAN,P38398\n
## 6 Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180).\n BRCA2_HUMAN,P51587\n
## 7 Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:9837883, PubMed:10587439, PubMed:10529171). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (PubMed:9837883, PubMed:10587439). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (PubMed:8627182, PubMed:9792674, PubMed:8195247). May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis (PubMed:8107690).\n CCL2_HUMAN,P13500\n
## 8 Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells (PubMed:11976333). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.\n CADH1_HUMAN,P12830\n
## 9 Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces (PubMed:21285368, PubMed:25402769). Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of the complement amplification loop (PubMed:19503104). As a cofactor of the serine protease factor I, CFH also regulates proteolytic degradation of already-deposited C3b (PubMed:18252712, PubMed:28671664). In addition, mediates several cellular responses through interaction with specific receptors. For example, interacts with CR3/ITGAM receptor and thereby mediates the adhesion of human neutrophils to different pathogens. In turn, these pathogens are phagocytosed and destroyed (PubMed:9558116, PubMed:20008295).\n CFAH_HUMAN,P08603\n
## 10 Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity).\n CTNB1_HUMAN,P35222\n
## 11 IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.\n IL8_HUMAN,P10145\n
## 12 Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.\n ERBB2_HUMAN,P04626\n
## 13 Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151).\n RASH_HUMAN,P01112\n
## 14 Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.\n IFNG_HUMAN,P01579\n
## 15 Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3 (PubMed:16982608). In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators (PubMed:18025162). Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha (PubMed:1940799, PubMed:7512027, PubMed:11564774). Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation (PubMed:8144879). In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling (By similarity).\n IL10_HUMAN,P22301\n
## 16 Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells (PubMed:10653850).\n IL1B_HUMAN,P01584\n
## 17 Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.\n IL6_HUMAN,P05231\n
## 18 Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the regulation of cell proliferation (PubMed:23698361, PubMed:22711838). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306).\n RASK_HUMAN,P01116\n
## 19 The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.\n MUC1_HUMAN,P15941\n
## 20 Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.\n RASN_HUMAN,P01111\n
## 21 Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Also has serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity).\n PK3CA_HUMAN,P42336\n
## 22 Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4 (PubMed:26504226, PubMed:16824732). The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.\n PTEN_HUMAN,P60484\n
## 23 Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918, PubMed:16829952, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity).\n TNFA_HUMAN,P01375\n
## 24 Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492).\n P53_HUMAN,P04637\n
## 25 Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity).\n VEGFA_HUMAN,P15692\n
## todaysDate UL_GSM9093 UL_GSM9094 UL_GSM9095 UL_GSM9096
## 1 Tue Aug 04 12:03:20 2020 16.00000 31.50000 18.80000 17.40000
## 2 Tue Aug 04 12:03:08 2020 251.20000 160.40000 192.70000 235.20000
## 3 Tue Aug 04 12:03:14 2020 409.40000 81.36667 74.63333 179.73333
## 4 Tue Aug 04 12:03:10 2020 25.10000 74.50000 27.40000 63.90000
## 5 Tue Aug 04 12:02:55 2020 14.60000 31.05000 33.65000 37.95000
## 6 Tue Aug 04 12:02:58 2020 7.35000 17.55000 11.35000 16.20000
## 7 Tue Aug 04 12:03:06 2020 98.20000 51.50000 87.30000 7.50000
## 8 Tue Aug 04 12:03:13 2020 13.60000 8.25000 17.75000 12.60000
## 9 Tue Aug 04 12:03:18 2020 69.80000 57.85000 82.55000 47.40000
## 10 Tue Aug 04 12:03:09 2020 1022.80000 1591.30000 1054.30000 877.10000
## 11 Tue Aug 04 12:03:21 2020 5.95000 21.20000 14.65000 16.95000
## 12 Tue Aug 04 12:03:03 2020 98.60000 79.20000 66.90000 95.90000
## 13 Tue Aug 04 12:03:16 2020 195.50000 88.60000 136.10000 107.30000
## 14 Tue Aug 04 12:03:02 2020 15.90000 31.10000 49.40000 27.70000
## 15 Tue Aug 04 12:02:54 2020 40.80000 4.70000 27.40000 16.20000
## 16 Tue Aug 04 12:02:56 2020 42.20000 62.00000 49.35000 47.25000
## 17 Tue Aug 04 12:03:05 2020 29.10000 35.80000 46.50000 43.50000
## 18 Tue Aug 04 12:03:00 2020 108.60000 290.16667 232.60000 162.60000
## 19 Tue Aug 04 12:03:11 2020 36.06667 47.76667 49.26667 33.46667
## 20 Tue Aug 04 12:03:19 2020 109.40000 54.80000 39.40000 43.70000
## 21 Tue Aug 04 12:02:57 2020 124.60000 96.50000 114.50000 108.20000
## 22 Tue Aug 04 12:03:04 2020 164.17500 106.37500 119.62500 150.87500
## 23 Tue Aug 04 12:02:52 2020 43.40000 35.90000 42.70000 33.40000
## 24 Tue Aug 04 12:02:51 2020 114.30000 120.90000 78.70000 93.45000
## 25 Tue Aug 04 12:03:17 2020 422.40000 200.75000 313.70000 290.22500
## UL_GSM9097 nonUL_GSM9098 nonUL_GSM9099 nonUL_GSM9100 nonUL_GSM9101
## 1 42.30000 25.60000 2.9000 19.90000 8.2000
## 2 193.90000 146.00000 145.0000 230.00000 201.0000
## 3 234.16667 162.90000 185.0000 277.56667 132.2667
## 4 41.40000 62.80000 26.2000 50.90000 44.0000
## 5 38.65000 18.95000 9.5000 15.95000 27.8000
## 6 10.55000 13.65000 21.5000 8.10000 11.9000
## 7 7.80000 530.40000 720.5000 346.30000 51.9000
## 8 3.15000 20.20000 109.6500 7.60000 35.8000
## 9 39.00000 90.60000 45.5000 90.05000 131.2000
## 10 539.50000 1140.20000 530.5000 993.00000 537.4000
## 11 11.00000 319.35000 28.7000 9.85000 17.2000
## 12 82.00000 54.90000 139.4500 125.80000 129.2500
## 13 140.40000 99.80000 123.7000 117.30000 142.9000
## 14 42.70000 50.20000 27.5000 29.20000 24.3000
## 15 36.10000 37.10000 27.7000 25.80000 10.9000
## 16 76.10000 175.15000 64.4000 33.25000 71.6000
## 17 61.10000 617.60000 72.1000 76.60000 43.5000
## 18 178.73333 129.50000 130.2333 145.56667 110.3333
## 19 42.43333 44.16667 199.9333 79.13333 85.9000
## 20 56.60000 74.40000 107.0000 65.90000 59.0000
## 21 66.40000 154.90000 178.3000 141.80000 132.2000
## 22 136.17500 141.27500 114.0500 125.75000 140.8000
## 23 49.00000 47.20000 41.7000 28.00000 61.5000
## 24 80.25000 91.75000 48.6500 78.75000 77.2000
## 25 169.62500 638.85000 719.1750 712.27500 701.8500
## nonUL_GSM9102 UL_mean nonUL_mean UL_foldChange
## 1 15.300 25.200 14.38000 1.7524339
## 2 192.700 206.680 182.94000 1.1297693
## 3 185.300 195.860 188.60667 1.0384575
## 4 31.300 46.460 43.04000 1.0794610
## 5 27.850 31.180 20.01000 1.5582209
## 6 8.850 12.600 12.80000 0.9843750
## 7 132.400 50.460 356.30000 0.1416222
## 8 5.400 11.070 35.73000 0.3098237
## 9 163.000 59.320 104.07000 0.5700010
## 10 457.300 1017.000 731.68000 1.3899519
## 11 10.250 13.950 77.07000 0.1810043
## 12 83.050 84.520 106.49000 0.7936895
## 13 133.200 133.580 123.38000 1.0826714
## 14 30.700 33.360 32.38000 1.0302656
## 15 37.600 25.040 27.82000 0.9000719
## 16 57.850 55.380 80.45000 0.6883779
## 17 103.300 43.200 182.62000 0.2365568
## 18 136.100 194.540 130.34667 1.4924816
## 19 81.000 41.800 98.02667 0.4264146
## 20 62.500 60.780 73.76000 0.8240239
## 21 167.800 102.040 155.00000 0.6583226
## 22 162.550 135.445 136.88500 0.9894802
## 23 26.800 40.880 41.04000 0.9961014
## 24 74.600 97.520 74.19000 1.3144629
## 25 657.825 279.340 685.99500 0.4072041Lets do the same for the flu data.
Flu1 <- FluImz_1day %>% filter(FluImz_1day$Gene.Symbol %in% serousList)
Flu1_df <- Flu1 %>% group_by(Gene.Symbol) %>% summarise_at(vars('Flu.Immunized.Only.Day.1':'Flu.Immunized.Only.Day.1.2'),mean)
Flu1_df## # A tibble: 22 x 4
## Gene.Symbol Flu.Immunized.Only.D~ Flu.Immunized.Only.D~ Flu.Immunized.Only.D~
## <chr> <dbl> <dbl> <dbl>
## 1 AFP 3.09 2.60 2.69
## 2 AKT1 7.02 6.95 6.98
## 3 APOE 2.55 2.67 2.99
## 4 BRAF 3.93 4.42 4.49
## 5 BRCA1 3.57 3.52 3.36
## 6 BRCA2 2.63 2.43 2.73
## 7 CCL2 3.25 3.20 2.44
## 8 CDH1 2.68 2.74 3.10
## 9 CFH 2.97 4.32 3.61
## 10 CTNNB1 7.77 7.99 7.93
## # ... with 12 more rowsFlu7 <- FluImz_7day %>% filter(FluImz_7day$Gene.Symbol %in% serousList)
Flu7_df <- Flu7 %>% group_by(Gene.Symbol) %>% summarise_at(vars('Flu.Immunized.Only.Day.7':'Flu.Immunized.Only.Day.7.2'),mean)
Flu7_df## # A tibble: 22 x 4
## Gene.Symbol Flu.Immunized.Only.D~ Flu.Immunized.Only.D~ Flu.Immunized.Only.D~
## <chr> <dbl> <dbl> <dbl>
## 1 AFP 2.43 2.25 2.31
## 2 AKT1 6.98 7.10 6.79
## 3 APOE 2.89 2.88 2.79
## 4 BRAF 4.80 4.66 4.82
## 5 BRCA1 3.29 3.10 3.23
## 6 BRCA2 2.69 2.66 2.55
## 7 CCL2 5.21 6.93 3.25
## 8 CDH1 2.66 3.01 2.64
## 9 CFH 2.81 3.19 3.25
## 10 CTNNB1 7.91 8.20 7.71
## # ... with 12 more rowsnonImm <- healthy_noFluImz %>% filter(healthy_noFluImz$Gene.Symbol %in% serousList)
nonImm_df <- nonImm %>% group_by(Gene.Symbol) %>% summarise_at(vars('Flu.non.immunized.healthy':'Flu.non.immunized.healthy.5'),mean)
nonImm## Gene.Symbol Flu.non.immunized.healthy Flu.non.immunized.healthy.1
## 1 AFP 2.841813 3.073922
## 2 AKT1 7.471751 7.023180
## 3 APOE 3.340333 3.383444
## 4 BRAF 4.954855 4.757742
## 5 BRCA1 3.833138 4.232549
## 6 BRCA2 3.111340 3.295374
## 7 CCL2 2.943400 3.020114
## 8 CDH1 3.265606 3.381843
## 9 CFH 3.717802 3.762299
## 10 CTNNB1 8.215586 8.127681
## 11 ERBB2 3.536601 3.574591
## 12 HRAS 6.467575 5.855811
## 13 IFNG 4.368996 4.078136
## 14 IL10 3.045313 3.073922
## 15 IL1B 5.424972 5.598697
## 16 IL6 3.532791 3.506112
## 17 KRAS 6.928380 6.705617
## 18 MUC1 3.520380 3.364636
## 19 NRAS 8.202526 8.191656
## 20 PIK3CA 6.521786 6.625757
## 21 TNF 4.389836 4.684353
## 22 VEGFA 5.801427 5.061772
## Flu.non.immunized.healthy.2 Flu.non.immunized.healthy.3
## 1 3.271753 2.466269
## 2 7.202321 7.006535
## 3 3.598646 2.726161
## 4 5.259674 4.452476
## 5 4.031393 3.342950
## 6 3.144021 2.578839
## 7 2.996591 5.582259
## 8 3.286248 2.662666
## 9 4.333678 3.635098
## 10 8.240825 7.837355
## 11 3.080208 3.003460
## 12 6.383811 5.838683
## 13 4.808612 4.312713
## 14 3.916677 2.552231
## 15 7.833018 12.813665
## 16 3.862225 10.847922
## 17 6.931805 5.922192
## 18 3.574183 3.235098
## 19 8.466111 7.467286
## 20 6.559634 5.686797
## 21 4.164460 10.577193
## 22 6.724921 4.735396
## Flu.non.immunized.healthy.4 Flu.non.immunized.healthy.5
## 1 2.737931 2.465670
## 2 7.283670 6.763728
## 3 2.703655 2.801232
## 4 3.869999 4.515253
## 5 4.264876 3.407837
## 6 2.748326 2.475685
## 7 3.973207 2.856823
## 8 2.710926 2.772311
## 9 3.032385 2.969977
## 10 7.459086 7.860346
## 11 2.980136 2.908465
## 12 6.146104 5.982502
## 13 4.101681 4.677779
## 14 2.596116 2.659251
## 15 12.465921 9.889004
## 16 7.352172 6.917782
## 17 5.718022 5.911121
## 18 3.124663 3.095370
## 19 7.450502 7.395234
## 20 5.626983 6.487241
## 21 11.131047 6.265858
## 22 4.485716 5.131598Flu1_df <- as.data.frame(Flu1_df)
row.names(Flu1_df) <- Flu1_df$Gene.Symbol
Flu7_df <- as.data.frame(Flu7_df)
row.names(Flu7_df) <- Flu7_df$Gene.Symbol
NonImm_df <- as.data.frame(nonImm)
row.names(NonImm_df) <- nonImm$Gene.Symbol
Flu1_DF <- Flu1_df[,c(2:4)]
Flu7_DF <- Flu7_df[,c(2:4)]
NonImm_df <- NonImm_df[,c(c(2:7))]
colnames(Flu1_DF) <- c('flu_1day_sample1','flu_1day_sample2','flu_1day_sample3')
colnames(Flu7_DF) <- c('flu_7day_sample1','flu_7day_sample2','flu_7day_sample3')
colnames(NonImm_df) <- c('nonImmunized_sample1',
'nonImmunized_sample2',
'nonImmunized_sample3',
'nonImmunized_sample4',
'nonImmunized_sample5',
'nonImmunized_sample6')
Flu1_DF$flu_1day_mean <- apply(Flu1_DF,1,mean)
Flu7_DF$flu_7day_mean <- apply(Flu7_DF,1,mean)
NonImm_df$nonImm_healthy_mean <- apply(NonImm_df,1,mean)
Flu1_DF$gene <- row.names(Flu1_DF)
Flu7_DF$gene <- row.names(Flu7_DF)
NonImm_df$gene <- row.names(NonImm_df)fludf <- merge(Flu1_DF, Flu7_DF, by.x='gene', by.y='gene')
FLUDF <- merge(fludf,NonImm_df, by.x='gene', by.y='gene')FLU_UL_DF <- merge(ULDF,FLUDF, by.x='gene', by.y='gene')
colnames(FLU_UL_DF)## [1] "gene" "proteinSearched" "EntrezSummary"
## [4] "GeneCardsSummary" "UniProtKB_Summary" "todaysDate"
## [7] "UL_GSM9093" "UL_GSM9094" "UL_GSM9095"
## [10] "UL_GSM9096" "UL_GSM9097" "nonUL_GSM9098"
## [13] "nonUL_GSM9099" "nonUL_GSM9100" "nonUL_GSM9101"
## [16] "nonUL_GSM9102" "UL_mean" "nonUL_mean"
## [19] "UL_foldChange" "flu_1day_sample1" "flu_1day_sample2"
## [22] "flu_1day_sample3" "flu_1day_mean" "flu_7day_sample1"
## [25] "flu_7day_sample2" "flu_7day_sample3" "flu_7day_mean"
## [28] "nonImmunized_sample1" "nonImmunized_sample2" "nonImmunized_sample3"
## [31] "nonImmunized_sample4" "nonImmunized_sample5" "nonImmunized_sample6"
## [34] "nonImm_healthy_mean"Flu_UL_DF <- FLU_UL_DF[,c(1:19,20:22,24:26,28:33,23,27,34)]
Flu_UL_DF$flu_1day_foldChange <- Flu_UL_DF$flu_1day_mean/Flu_UL_DF$nonImm_healthy_mean
Flu_UL_DF$flu_7day_foldChange <- Flu_UL_DF$flu_7day_mean/Flu_UL_DF$nonImm_healthy_mean
head(Flu_UL_DF)## gene proteinSearched
## 1 AFP serous-fluid
## 2 AKT1 serous-fluid
## 3 APOE serous-fluid
## 4 BRAF serous-fluid
## 5 BRCA1 serous-fluid
## 6 BRCA2 serous-fluid
## EntrezSummary
## 1 This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing advanced gastric cancer. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. [provided by RefSeq, Oct 2019]
## 2 The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]
## 3 The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]
## 4 This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]
## 5 This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]
## 6 Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]
## GeneCardsSummary
## 1 AFP (Alpha Fetoprotein) is a Protein Coding gene. Diseases associated with AFP include Alpha-Fetoprotein Deficiency and Alpha-Fetoprotein, Hereditary Persistence Of. Among its related pathways are FOXA2 and FOXA3 transcription factor networks and Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers. An important paralog of this gene is ALB.
## 2 AKT1 (AKT Serine/Threonine Kinase 1) is a Protein Coding gene. Diseases associated with AKT1 include Proteus Syndrome and Cowden Syndrome 6. Among its related pathways are Regulation of TP53 Activity through Acetylation and Association Between Physico-Chemical Features and Toxicity Associated Pathways. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is AKT3.
## 3 APOE (Apolipoprotein E) is a Protein Coding gene. Diseases associated with APOE include Lipoprotein Glomerulopathy and Hyperlipoproteinemia, Type Iii. Among its related pathways are Neuroscience and Lipoprotein metabolism. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and signaling receptor binding. An important paralog of this gene is APOA4.
## 4 BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with BRAF include Cardiofaciocutaneous Syndrome 1 and Lung Cancer. Among its related pathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and Negative regulation of MAPK pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is RAF1.
## 5 BRCA1 (BRCA1 DNA Repair Associated) is a Protein Coding gene. Diseases associated with BRCA1 include Breast-Ovarian Cancer, Familial 1 and Fanconi Anemia, Complementation Group S. Among its related pathways are ATM Pathway and Homologous DNA Pairing and Strand Exchange. Gene Ontology (GO) annotations related to this gene include RNA binding and ligase activity.
## 6 BRCA2 (BRCA2 DNA Repair Associated) is a Protein Coding gene. Diseases associated with BRCA2 include Fanconi Anemia, Complementation Group D1 and Breast Cancer. Among its related pathways are Homologous DNA Pairing and Strand Exchange and Meiosis. Gene Ontology (GO) annotations related to this gene include protease binding and histone acetyltransferase activity.
## UniProtKB_Summary
## 1 Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties.\n FETA_HUMAN,P02771\n
## 2 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174, PubMed:20231902). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768).\n AKT1_HUMAN,P31749\n
## 3 APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:6860692, PubMed:1911868, PubMed:14754908). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:6860692, PubMed:2762297, PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908, PubMed:23620513). Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:6860692, PubMed:2762297, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:6860692, PubMed:1911868). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:2762297, PubMed:1917954, PubMed:7768901, PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194, PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945). Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:9395455, PubMed:9488694, PubMed:23676495, PubMed:7635945). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:23676495, PubMed:29516132). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues (PubMed:2762297, PubMed:29516132). By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:2762297, PubMed:1917954, PubMed:29516132). APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis (PubMed:9395455, PubMed:14754908, PubMed:23620513). First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513). Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes (PubMed:9395455). APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting (PubMed:8939961, PubMed:25173806). APOE in also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). APOE, may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP (PubMed:28111074).\n APOE_HUMAN,P02649\n
## 4 Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179).\n BRAF_HUMAN,P15056\n
## 5 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator (PubMed:20160719).\n BRCA1_HUMAN,P38398\n
## 6 Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180).\n BRCA2_HUMAN,P51587\n
## todaysDate UL_GSM9093 UL_GSM9094 UL_GSM9095 UL_GSM9096
## 1 Tue Aug 04 12:03:20 2020 16.00 31.50000 18.80000 17.4000
## 2 Tue Aug 04 12:03:08 2020 251.20 160.40000 192.70000 235.2000
## 3 Tue Aug 04 12:03:14 2020 409.40 81.36667 74.63333 179.7333
## 4 Tue Aug 04 12:03:10 2020 25.10 74.50000 27.40000 63.9000
## 5 Tue Aug 04 12:02:55 2020 14.60 31.05000 33.65000 37.9500
## 6 Tue Aug 04 12:02:58 2020 7.35 17.55000 11.35000 16.2000
## UL_GSM9097 nonUL_GSM9098 nonUL_GSM9099 nonUL_GSM9100 nonUL_GSM9101
## 1 42.3000 25.60 2.9 19.9000 8.2000
## 2 193.9000 146.00 145.0 230.0000 201.0000
## 3 234.1667 162.90 185.0 277.5667 132.2667
## 4 41.4000 62.80 26.2 50.9000 44.0000
## 5 38.6500 18.95 9.5 15.9500 27.8000
## 6 10.5500 13.65 21.5 8.1000 11.9000
## nonUL_GSM9102 UL_mean nonUL_mean UL_foldChange flu_1day_sample1
## 1 15.30 25.20 14.3800 1.752434 3.091881
## 2 192.70 206.68 182.9400 1.129769 7.017981
## 3 185.30 195.86 188.6067 1.038457 2.546745
## 4 31.30 46.46 43.0400 1.079461 3.926995
## 5 27.85 31.18 20.0100 1.558221 3.565998
## 6 8.85 12.60 12.8000 0.984375 2.627580
## flu_1day_sample2 flu_1day_sample3 flu_7day_sample1 flu_7day_sample2
## 1 2.598148 2.693907 2.431215 2.253567
## 2 6.953327 6.982354 6.980820 7.102669
## 3 2.668470 2.986834 2.888725 2.882127
## 4 4.419892 4.494043 4.797350 4.662446
## 5 3.524617 3.362609 3.292334 3.103902
## 6 2.431320 2.729531 2.687913 2.655226
## flu_7day_sample3 nonImmunized_sample1 nonImmunized_sample2
## 1 2.312690 2.841813 3.073922
## 2 6.788185 7.471751 7.023180
## 3 2.789642 3.340333 3.383444
## 4 4.820254 4.954855 4.757742
## 5 3.234686 3.833138 4.232549
## 6 2.551580 3.111340 3.295374
## nonImmunized_sample3 nonImmunized_sample4 nonImmunized_sample5
## 1 3.271753 2.466269 2.737931
## 2 7.202321 7.006535 7.283670
## 3 3.598646 2.726161 2.703655
## 4 5.259674 4.452476 3.869999
## 5 4.031393 3.342950 4.264876
## 6 3.144021 2.578839 2.748326
## nonImmunized_sample6 flu_1day_mean flu_7day_mean nonImm_healthy_mean
## 1 2.465670 2.794645 2.332490 2.809560
## 2 6.763728 6.984554 6.957225 7.125197
## 3 2.801232 2.734016 2.853498 3.092245
## 4 4.515253 4.280310 4.760017 4.635000
## 5 3.407837 3.484408 3.210307 3.852124
## 6 2.475685 2.596144 2.631573 2.892264
## flu_1day_foldChange flu_7day_foldChange
## 1 0.9946915 0.8301978
## 2 0.9802611 0.9764255
## 3 0.8841525 0.9227916
## 4 0.9234758 1.0269724
## 5 0.9045420 0.8333863
## 6 0.8976164 0.9098660write.csv(Flu_UL_DF,'Flu_UL_df.csv', row.names=FALSE)
write.csv(ULDF, 'ULDF.csv', row.names=FALSE)
write.csv(FLUDF, 'FLUDF.csv', row.names=FALSE)I created those tables above to create visualizations in Tableau separately.
We have gone through 10 of the 25 genes we gathered from genecards.org on serous fluid genes. We still want to look at the connective tissue genes, like the clast and blast cells and the blood genes. Lets skip the other 15 genes and look at the genes that are in the clast and blast genes and ertyrocytes and thrombocytes. We have seen many leukocytes like the interleukin genes above.
find25genes('clast')getProteinGenes('clast')clast <- read.csv('Top25clasts.csv')
for (i in clast$proteinType){
getSummaries(i,'clast')
}getGeneSummaries('clast')clastSumms <- read.csv('proteinGeneSummaries_clast.csv')Lets now get the Entrez summary of the first clast gene. These genes are associated with clast cells that break up damaged scar tissue and waste in the body so that blast cells can build and repair the cells.
The first cell is CTSK.
clastSumms[1,3]## [1] The protein encoded by this gene is a lysosomal cysteine proteinase involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is predominantly expressed in osteoclasts. However, the encoded protein is also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature. [provided by RefSeq, Apr 2013]
## 6 Levels: IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3. ...The above Entrez summary says this gene clast, CTSK, is involved in bone remodeling and resorption. It suggests this gene is responsible for breast cancer invasiveness because there are a significant number of cases this protein was found in that tissue. If the significance level is 5% then it is in 5% of cases, but the level of significance wasn’t stated so it could be 5% or even more than 50% of cases. Also short height and osteosclerosis which is bone hardening and higher than normal bone density. Similar to artherosclerosis or artery hardening.
Lets see how the UL and flu immunizations’ gene expression of CTSK behave compared to healthy samples by looking at the fold change ratio.
UL fold change to healthy of CTSK:
getMeanMedian('CTSK')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.247707
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.151987## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 1978 2524.5 922.8 732.9 1272 1201.2 1330.68
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 1978 1236.6 1.247707 1.151987
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 1978 1377 973.1 1080.4 1093.1 808.9
## mean _nonUL median _nonUL
## 1978 1066.5 1073.45There is an over expression of this osteo clast gene, CTSK, in UL compared to non-UL samples by 15-24%.
Now for the Flu immunizations after 1 day samples of CTSK:
getMeanMedianFlu1('CTSK')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9856621
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9896585## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 2425 6.064636 5.74881
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 2425 6.047708 5.953718 6.000713
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 2425 0.9856621 0.9896585
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 2425 6.063418
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 2425 6.220545
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 2425 6.686647
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 2425 5.560045
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 2425 5.449586
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 2425 6.261702 6.040324
## median _healthyNonImmz
## 2425 6.063418There is not much change in the CTSK osteoclast gene in the flu immunized samples after 1 day compared to non-immunized and healthy samples.However, the change is in the negative direction or shows a decrease or under expression in CTSK of 1.1-1.4%
How about the flu immunized samples after 7 days for CTSK fold changes?
getMeanMedianFlu7('CTSK')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 1.019701
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 1.007476## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 2425 5.951991 6.467807
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 2425 6.058175 6.159325 6.10875
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 2425 1.019701 1.007476
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 2425 6.063418
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 2425 6.220545
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 2425 6.686647
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 2425 5.560045
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 2425 5.449586
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 2425 6.261702 6.040324
## median _healthyNonImmz
## 2425 6.063418There is also not much change in the flu immunized samples after 7 days of being immunized, but the change is in the elevated direction by .7-2% increased in CTSK.
The next clast gene is ACP5, lets look at the uniprotkb gene summary instead of the entrez summary:
clastSumms[2,5]## [1] Involved in osteopontin/bone sialoprotein dephosphorylation. Its expression seems to increase in certain pathological states such as Gaucher and Hodgkin diseases, the hairy cell, the B-cell, and the T-cell leukemias.\n PPA5_HUMAN,P13686\n
## 6 Levels: IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.\n IBP5_HUMAN,P24593\n ...This clast gene, ACP5, is increased in certain diseases like Lymphoma and Leukemia. Lets see how it behaves in UL and flu immunized samples.
ACP5 in UL:
getMeanMedian('ACP5')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.032629
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.119614## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 4165 73.3 127 77.4 105.5 110.5 98.74
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 4165 102.12 1.032629 1.119614
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 4165 139.3 80.8 71.1 100.1 86.8
## mean _nonUL median _nonUL
## 4165 95.62 91.21In UL, the ACP5 gene is increased in gene expression from 3.2-11.9 %.
ACP5 in Flu immunized samples after 1 day:
getMeanMedianFlu1('ACP5')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9707761
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 1.013018## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 125 4.641301 5.382067
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 125 5.416786 5.146718 5.264392
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 125 0.9707761 1.013018
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 125 6.252937
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 125 5.422787
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 125 5.068705
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 125 4.744956
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 125 5.123792
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 125 5.19674 5.301653
## median _healthyNonImmz
## 125 5.19674In flu immunized samples after 1 day, the gene expression is slightly decreased in ACP5 by 2% to an increase of 1.3%, not by much change.
Now for the flu immunized samples after 7 days:
getMeanMedianFlu7('ACP5')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 1.029442
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 1.032164## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 125 5.160605 5.270027
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 125 5.942606 5.457746 5.363887
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 125 1.029442 1.032164
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 125 6.252937
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 125 5.422787
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 125 5.068705
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 125 4.744956
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 125 5.123792
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 125 5.19674 5.301653
## median _healthyNonImmz
## 125 5.19674After 7 days, ACP5 is slightly increased in gene expression by 2.9-3.2%
The third of our six clast associated genes is IGF1, lets get the uniprotkb summary:
clastSumms[3,5]## [1] The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity). Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiatiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:19578119, PubMed:22351760, PubMed:23696648, PubMed:23243309).\n IGF1_HUMAN,P05019\n
## 6 Levels: IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.\n IBP5_HUMAN,P24593\n ...The above gene summary of IGF1 sounds like it provides the energy needed to convert calories from glucose for clasts to have energy to work.
Lets see how IGF1 behaves in UL samples:
getMeanMedian('IGF1')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.421990 1.149582 1.409588 1.503734
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.829446 1.270024 1.496127 1.521342## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 9033 1638.1 534.6 387.6 1529.7 1533.4 1124.68
## 9034 1955.6 972.1 620.4 1701.8 1426.3 1335.24
## 9035 2251.6 957.4 377.5 1002.3 1312.3 1180.22
## 10982 1265.1 881.5 286.6 610.1 1064.0 821.46
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 9033 1327.19 1.421990 1.829446
## 9034 1380.77 1.149582 1.270024
## 9035 1091.26 1.409588 1.496127
## 10982 851.48 1.503734 1.521342
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 9033 449.8 1301.7 940.6 602.5
## 9034 602.8 1693.7 1553.2 944.9
## 9035 336.6 1460.4 1187.9 580.0
## 10982 251.0 791.6 573.1 488.3
## GSM9102 _nonUL mean _nonUL median _nonUL
## 9033 660.0 790.92 725.46
## 9034 1012.9 1161.50 1087.20
## 9035 621.5 837.28 729.39
## 10982 627.4 546.28 559.69The UL fold change values are significantly shown to increase in UL compared to non-UL samples for IGF1 by 14-83%, with an approximate average increase of 40%.The UL is using this clast gene energy source or requesting more of this clast gene to supply it the energy it needs.
In flu 1 day immunized for IGF1:
getMeanMedianFlu1('IGF2')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## numeric(0)
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## numeric(0)## [[1]]
## [1] Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## [3] Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day
## [5] median _flu_1day FoldChange_mean _flu_1day
## [7] FoldChange_median _flu_1day
## <0 rows> (or 0-length row.names)
##
## [[2]]
## [1] Flu.non.immunized.healthy _healthyNonImmz
## [2] Flu.non.immunized.healthy.1 _healthyNonImmz
## [3] Flu.non.immunized.healthy.2 _healthyNonImmz
## [4] Flu.non.immunized.healthy.3 _healthyNonImmz
## [5] Flu.non.immunized.healthy.4 _healthyNonImmz
## [6] Flu.non.immunized.healthy.5 _healthyNonImmz
## [7] mean _healthyNonImmz
## [8] median _healthyNonImmz
## <0 rows> (or 0-length row.names)This gene isn’t in the flu sampls so no point in trying the 7 day immunized subset for IGF1.
The next gene, or fourth gene of six clast genes is IGFBP2, lets use the Entrez gene summary.
clastSumms[4,3]## [1] The protein encoded by this gene is one of six similar proteins that bind insulin-like growth factors I and II (IGF-I and IGF-II). The encoded protein can be secreted into the bloodstream, where it binds IGF-I and IGF-II with high affinity, or it can remain intracellular, interacting with many different ligands. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the patient. Several transcript variants, one encoding a secreted isoform and the others encoding nonsecreted isoforms, have been found for this gene. [provided by RefSeq, Sep 2015]
## 6 Levels: IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3. ...The summary above says that IGFBP2 is associated with many tumors and promotes cell growth of several ligands.
Lets see how IGFBP2 behaves in UL:
getMeanMedian('IGFBP2')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.8904992
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.4662011## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 2246 2224.7 352.9 182.6 417.4 429.1 721.34
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 2246 423.25 0.8904992 0.4662011
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 2246 104.4 1005.7 1024 1189.2 726.9
## mean _nonUL median _nonUL
## 2246 810.04 907.87In UL samples the IGFBP2 clast gene is under expressed 11-54%, which indicates that though it is responsible for many tumors in the body, benign UL are not tumors that grow using this clast gene. Also, lets look at the genecards summary instead of the entrez summary and we will see that IGFBP2 is also an indicative marker for malignant or cancerous ovarian cysts.
clastSumms[4,4]## [1] IGFBP2 (Insulin Like Growth Factor Binding Protein 2) is a Protein Coding gene. Diseases associated with IGFBP2 include Malignant Ovarian Cyst and Insulin-Like Growth Factor I. Among its related pathways are Hematopoietic Stem Cells and Lineage-specific Markers and Myometrial Relaxation and Contraction Pathways. Gene Ontology (GO) annotations related to this gene include insulin-like growth factor binding and insulin-like growth factor II binding. An important paralog of this gene is IGFBP4.
## 6 Levels: ACP5 (Acid Phosphatase 5, Tartrate Resistant) is a Protein Coding gene. Diseases associated with ACP5 include Spondyloenchondrodysplasia With Immune Dysregulation and Spondyloenchondrodysplasia. Among its related pathways are Lysosome and ATP/ITP metabolism. Gene Ontology (GO) annotations related to this gene include hydrolase activity and ferric iron binding. ...So, this also reaffirms the benign nature of ULs or uterine tumors, and adds that they are not related to ovarian cancer.
IGFBP2 in flu 1 day:
getMeanMedianFlu1('IGFBP2')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 1.076218
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9837015## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 5040 2.955331 5.051288
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 5040 2.700175 3.568931 3.262131
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 5040 1.076218 0.9837015
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5040 3.414449
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5040 3.563854
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5040 3.155143
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5040 2.676249
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5040 4.38578
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5040 2.701603 3.31618
## median _healthyNonImmz
## 5040 3.31618After one day of flu immunizations the fold change ranges from -2% to 7%. Not a huge increase or decrease. Lets compare these values to the 7 day immunized flu samples.
IGFBP2 in flu 7 days:
getMeanMedianFlu7('IGFBP2')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.9576333
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.8926931## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 5040 2.647678 4.134396
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 5040 2.744978 3.175684 2.960331
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 5040 0.9576333 0.8926931
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5040 3.414449
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5040 3.563854
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5040 3.155143
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5040 2.676249
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5040 4.38578
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5040 2.701603 3.31618
## median _healthyNonImmz
## 5040 3.31618After 7 days of flu immunizations, there is no increase in IGFBP2 as there was after one day. There is a decrease in gene expression of 5-11%. This could mean there is no link to it feeding any growth needs for the body to clast cells, or not a need for energy in breaking down cellular waste after 7 days. It could also mean it isn’t significant to any changes that take place in the body fighting a deactivated flu antigen.
Our fifth clast gene is IGF2 with an Entrez gene summary of:
clastSumms[5,3]## [1] This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]
## 6 Levels: IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3. ...This gene is also an energy growth gene, but it is inherited from the father’s side of the genetic code or DNA of a person. The UniprotKB summary says this gene is related to fetal growth, and the genecards summary says it is on the same pathway network as cell death or apoptosis regulation. Lets see how this gene behaves in UL for IGF2.
IGF2 in UL:
getMeanMedian('IGF2')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 4.020800 7.267155 11.997389
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 4.256954 7.992300 14.849206## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 1937 2777.7 1596.1 1594.0 2062.0 2872.6 2180.48
## 1938 242.6 137.5 24.2 173.3 216.7 158.86
## 10335 112.2 95.2 26.9 84.1 141.1 91.90
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 1937 2121.24 4.020800 4.256954
## 1938 166.08 7.267155 7.992300
## 10335 93.55 11.997389 14.849206
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 1937 375.6 454.3 903.2 570.4
## 1938 4.7 9.6 27.3 48.0
## 10335 6.7 2.9 5.4 17.4
## GSM9102 _nonUL mean _nonUL median _nonUL
## 1937 408.0 542.30 498.30
## 1938 19.7 21.86 20.78
## 10335 5.9 7.66 6.30That is interesting that this gene with 3 different summaries for paternal inheritance, fetal growth, and cell death regulation for IGF2 displays fold change values of heightened increased values compared to non-UL samples. The increase or over expression is anywhere from 4-12 times the non-UL values or 400-1200% increased in UL.
IGF2 in flu 1 day:
getMeanMedianFlu1('IGF2')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## numeric(0)
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## numeric(0)## [[1]]
## [1] Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## [3] Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day
## [5] median _flu_1day FoldChange_mean _flu_1day
## [7] FoldChange_median _flu_1day
## <0 rows> (or 0-length row.names)
##
## [[2]]
## [1] Flu.non.immunized.healthy _healthyNonImmz
## [2] Flu.non.immunized.healthy.1 _healthyNonImmz
## [3] Flu.non.immunized.healthy.2 _healthyNonImmz
## [4] Flu.non.immunized.healthy.3 _healthyNonImmz
## [5] Flu.non.immunized.healthy.4 _healthyNonImmz
## [6] Flu.non.immunized.healthy.5 _healthyNonImmz
## [7] mean _healthyNonImmz
## [8] median _healthyNonImmz
## <0 rows> (or 0-length row.names)There is no IGF2 gene entry in our flu data, so there won’t be results for the 7 days immunized samples either.
Our last clast gene returned is IGFBP5, with an Entrez gene summary:
clastSumms[6,3]## [1] IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3.
## 6 Levels: IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3. ...The IGFBP5 gene cards summary:
clastSumms[6,4]## [1] IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3.
## 6 Levels: ACP5 (Acid Phosphatase 5, Tartrate Resistant) is a Protein Coding gene. Diseases associated with ACP5 include Spondyloenchondrodysplasia With Immune Dysregulation and Spondyloenchondrodysplasia. Among its related pathways are Lysosome and ATP/ITP metabolism. Gene Ontology (GO) annotations related to this gene include hydrolase activity and ferric iron binding. ...The IGFBP5 uniprotkb summary:
clastSumms[6,5]## [1] IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.\n IBP5_HUMAN,P24593\n
## 6 Levels: IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.\n IBP5_HUMAN,P24593\n ...The gene summaries for Entrez and gene cards is the same, for associated diseases of bone disease related to kidney disease and growth factor disease. The related gene pathways involve muscle contraction and relaxation and the pathway in cancer patients that cause their bodies to digest their muscles (autophagy) and senescing or cell death due to aging.
Lets see how IGFBP5 gene expression behaves in UL:
getMeanMedian('IGFBP5')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 1.316982 1.773503 1.505342 1.850598 1.772014
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 1.428429 1.740807 1.559563 1.989786 2.257877## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 2951 142.4 72.3 34.3 69.3 71.0 77.86
## 2952 402.8 208.7 250.8 231.7 288.8 276.56
## 2953 231.0 176.8 184.6 156.0 153.3 180.34
## 11345 773.5 692.5 819.1 868.6 732.0 777.14
## 11346 2819.7 4659.2 5532.8 5982.7 7416.4 5282.16
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 2951 71.65 1.316982 1.428429
## 2952 263.68 1.773503 1.740807
## 2953 178.57 1.505342 1.559563
## 11345 775.32 1.850598 1.989786
## 11346 5407.48 1.772014 2.257877
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 2951 41.2 90.5 92.7 37.4
## 2952 90.8 181.0 268.4 147.0
## 2953 70.8 145.2 180.0 109.2
## 11345 380.4 386.7 558.4 392.6
## 11346 1575.0 5006.0 4731.9 1809.0
## GSM9102 _nonUL mean _nonUL median _nonUL
## 2951 33.8 59.12 50.16
## 2952 92.5 155.94 151.47
## 2953 93.8 119.80 114.50
## 11345 381.6 419.94 389.65
## 11346 1782.5 2980.88 2394.94We can see an increase in gene expression of this clast gene, IGFBP5, in UL by 31-225% in UL compared to non-UL samples. This is significant and shows IGFBP5 has some role in UL pathogenesis or even growth. The uniprotkb gene summary says this gene can inhibit or stimulate the half life of the insulin growth factors and also alter the interactions on the cell surface receptors with IGFs or insulin growth factors.
Lets compare the flu immunized samples for IGFBP5.
getMeanMedianFlu1('IGFBP5')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9347759
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9414603## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 5043 2.721872 2.643726
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 5043 2.45375 2.606449 2.625087
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 5043 0.9347759 0.9414603
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5043 3.060145
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5043 3.061606
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5043 3.025399
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5043 2.526245
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5043 2.581708
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5043 2.474784 2.788314
## median _healthyNonImmz
## 5043 2.788314In flu immunized samples after 1 day, this gene IGFBP5 is under expressed by 6-7%.
Flu 7 days immunized:
getMeanMedianFlu7('IGFBP5')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.902281
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.905579## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 5043 2.540653 2.472641
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 5043 2.534235 2.515843 2.525039
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 5043 0.902281 0.905579
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5043 3.060145
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5043 3.061606
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5043 3.025399
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5043 2.526245
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5043 2.581708
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5043 2.474784 2.788314
## median _healthyNonImmz
## 5043 2.788314After 7 days of being immunized for the flu, IGFBP5 is under expressed by about 10%, that is less gene expression thand after 1 day. In fact the gene expression went from 5% under to 10% under in 7 days. This gene could possibly be blocked by other immunology genes that fight the flu virus and would possibly interfere with the process, so it is down regulated.
We have looked at the clast cells, six to be exact, in UL and immunized flu samples in 1 day and a week. Lets look at the blast cell genes now. These are the build and repair genes.
find25genes('blast')getProteinGenes('blast')For our blast genes we do have at least 25 genes returned, unlike our clast genes with only 6 genes returned.
Lets look at the gene summaries for these genes, or scrape them from the web to look at as we move through each blast gene in our analysis.
blast <- read.csv('Top25blasts.csv')for (i in blast$proteinType){
getSummaries(i,'blast')
}getGeneSummaries('blast')blastSumms <- read.csv('proteinGeneSummaries_blast.csv')The first gene is FLT3. I went over many of these 25 blast gene summaries and saw a majority of them are involved in hematopoeisis or blood cell formation and mutations in some genes are involved in leukemia and some other blood cancers. Also, in this list of 25 blast genes, TP53 and KRAs are included. We saw these genes earlier in our serous fluid list of 25 genes in the top 10 of that list. We won’t go through all of these 25 genes, but we will go over a few of them and their summaries. The Entrez FLT3 gene summary:
blastSumms[1,3]## [1] This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]
## 25 Levels: A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020] ...FLT3 in UL:
getMeanMedian('FLT3')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.8912037
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.9831871## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 6200 5.4 9.6 30.7 35.6 34.2 23.1
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 6200 26.9 0.8912037 0.9831871
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 6200 23.7 5.7 28.8 36.4 35
## mean _nonUL median _nonUL
## 6200 25.92 27.36There is an underexpression of FLT3 in UL by 2-11%.
FLT3 in flu 1 day:
getMeanMedianFlu1('FLT3')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## numeric(0)
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## numeric(0)## [[1]]
## [1] Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## [3] Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day
## [5] median _flu_1day FoldChange_mean _flu_1day
## [7] FoldChange_median _flu_1day
## <0 rows> (or 0-length row.names)
##
## [[2]]
## [1] Flu.non.immunized.healthy _healthyNonImmz
## [2] Flu.non.immunized.healthy.1 _healthyNonImmz
## [3] Flu.non.immunized.healthy.2 _healthyNonImmz
## [4] Flu.non.immunized.healthy.3 _healthyNonImmz
## [5] Flu.non.immunized.healthy.4 _healthyNonImmz
## [6] Flu.non.immunized.healthy.5 _healthyNonImmz
## [7] mean _healthyNonImmz
## [8] median _healthyNonImmz
## <0 rows> (or 0-length row.names)No results for FLT3 in the flu data.
The 2nd gene is KIT in our list of blast genes with an Entrez gene summary of:
blastSumms[2,3]## [1] This gene encodes a receptor tyrosine kinase. This gene was initially identified as a homolog of the feline sarcoma viral oncogene v-kit and is often referred to as proto-oncogene c-Kit. The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. This protein can be a membrane-bound or soluble protein. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]
## 25 Levels: A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020] ...I looked up a few terms with bing and found that gametogenesis is the process of cell splitting in creating gametes in meiosis and melanogenesis is the creation of melanin used in blocking sun rays and darker skin pigment and hair and iris of the eye pigmentation. This gene, KIT is said to phosphorylate many proteins involved in those two processes as well as blood cell formation, stem cell maintenance and cell migration and function and mast cell development. Mast cells carry basophils that are used in releasing histamine in immune responses to allergens and for inflamation in connective tissues. Phosphorylation is a way for cells to respond to external signals and stimuli and activate proteins or break them down structurally by residue or amino acid binding.
KIT blast gene in UL:
getMeanMedian('KIT')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.3999766
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.4637083## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 4578 66.2 89.1 84.2 34.4 68.6 68.5
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 4578 68.55 0.3999766 0.4637083
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL GSM9102 _nonUL
## 4578 119.4 282.6 102.4 124.4 227.5
## mean _nonUL median _nonUL
## 4578 171.26 147.83This gene is more than halfed in gene expression in UL compared to non-UL samples by 39-46%. The blast gene, KIT, doesn’t seem to be involved in ULs and this implies ULs do not use melanin, histamine, need meiosis, stem cell maintenance, or blood cell formation. Makes sense as those are created in the bone marrow typically.
KIT in flu 1 day:
getMeanMedianFlu1('KIT')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9187084
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9122892## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 5575 4.194594 4.128722
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 5575 4.43881 4.254042 4.224318
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 5575 0.9187084 0.9122892
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5575 4.774901
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5575 4.900217
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5575 4.46589
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5575 4.9432
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5575 4.584428
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5575 4.114119 4.630459
## median _healthyNonImmz
## 5575 4.630459The blast gene KIT is about 9% under expressed in flu immunized samples after 1 day.
KIT blast gene in flu 7 days:
getMeanMedianFlu7('KIT')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.925867
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.9433113## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 5575 4.448739 4.647864
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 5575 3.764965 4.28719 4.367964
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 5575 0.925867 0.9433113
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 5575 4.774901
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 5575 4.900217
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 5575 4.46589
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 5575 4.9432
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 5575 4.584428
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 5575 4.114119 4.630459
## median _healthyNonImmz
## 5575 4.630459The blast gene KIT is bout 6-8% under expressed in flu immunized samples after 7 days. Seems that the process to phosphorylate the inflammation and allergic immune response isn’t needed in flu immunized samples after 7 days.
Lets jump through the list of blast cells to some other genes that don’t involve blood cell creation or hematopeoisis. Lets jump to the 10th blast gene, ASXL1.
blastSumms[10,3]## [1] This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
## 25 Levels: A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020] ...The above Entrez gene summary for ASXL1 says it is a protein that could change the chromatin of localized areas and enhance transcription of certain genes and suppress others. DNA is wrapped tightly in chromatin and genes for proteins are mapped to certain chromosomes and expressed when the body needs them. This gene has mutations that are related to the blood cancer myelomonocytic leukemia.
getMeanMedian('ASXL1')## [1] "The foldchage of UL means to nonUL means is:"
## [1] 0.8816882 0.8682985 0.8897854
## [1] "The foldchage of UL medians to nonUL medians is:"
## [1] 0.8229900 0.8861789 0.8929388## [[1]]
## GSM9093 _UL GSM9094 _UL GSM9095 _UL GSM9096 _UL GSM9097 _UL mean _UL
## 11620 118.2 103.9 169.2 115.1 141.2 129.52
## 11623 206.8 228.9 187.0 155.9 172.1 190.14
## 11624 97.5 134.6 112.2 122.9 117.3 116.90
## median _UL FoldChange_mean _UL FoldChange_median _UL
## 11620 123.86 0.8816882 0.8229900
## 11623 188.57 0.8682985 0.8861789
## 11624 117.10 0.8897854 0.8929388
##
## [[2]]
## GSM9098 _nonUL GSM9099 _nonUL GSM9100 _nonUL GSM9101 _nonUL
## 11620 174.0 140.8 103.4 162.2
## 11623 257.0 206.6 206.5 202.2
## 11624 164.2 164.0 130.9 116.0
## GSM9102 _nonUL mean _nonUL median _nonUL
## 11620 154.1 146.90 150.50
## 11623 222.6 218.98 212.79
## 11624 81.8 131.38 131.14The blast gene ASXL1 is between 11-19% under expressed in UL tissue.
ASXL1 in flu 1 day:
getMeanMedianFlu1('ASXL1')## [1] "The foldchage of flu immunized after 1 day means to heathy non-immunized flu means is:"
## [1] 0.9479766
## [1] "The foldchage of flu immunized after 1 day medians to non-immunized flu medians is:"
## [1] 0.9302241## [[1]]
## Flu.Immunized.Only.Day.1 _flu_1day Flu.Immunized.Only.Day.1.1 _flu_1day
## 825 6.485773 6.724785
## Flu.Immunized.Only.Day.1.2 _flu_1day mean _flu_1day median _flu_1day
## 825 6.957184 6.722581 6.723683
## FoldChange_mean _flu_1day FoldChange_median _flu_1day
## 825 0.9479766 0.9302241
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 825 7.434443
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 825 7.228025
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 825 7.268164
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 825 6.815328
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 825 6.540595
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 825 7.262477 7.091505
## median _healthyNonImmz
## 825 7.228025The flu 1 day samples show an under expression of ASXL1 by 5-7%.
ASXL1 in flu 7 day samples:
getMeanMedianFlu7('ASXL1')## [1] "The foldchage of flu immunized after 7 days means to heathy non-immunized flu means is:"
## [1] 0.9718234
## [1] "The foldchage of flu immunized after 7 days medians to non-immunized flu medians is:"
## [1] 0.9475921## [[1]]
## Flu.Immunized.Only.Day.7 _flu_7day Flu.Immunized.Only.Day.7.1 _flu_7day
## 825 6.778113 6.806748
## Flu.Immunized.Only.Day.7.2 _flu_7day mean _flu_7day median _flu_7day
## 825 7.090211 6.891691 6.849219
## FoldChange_mean _flu_7day FoldChange_median _flu_7day
## 825 0.9718234 0.9475921
##
## [[2]]
## Flu.non.immunized.healthy _healthyNonImmz
## 825 7.434443
## Flu.non.immunized.healthy.1 _healthyNonImmz
## 825 7.228025
## Flu.non.immunized.healthy.2 _healthyNonImmz
## 825 7.268164
## Flu.non.immunized.healthy.3 _healthyNonImmz
## 825 6.815328
## Flu.non.immunized.healthy.4 _healthyNonImmz
## 825 6.540595
## Flu.non.immunized.healthy.5 _healthyNonImmz mean _healthyNonImmz
## 825 7.262477 7.091505
## median _healthyNonImmz
## 825 7.228025In the flu 7 day immunized samples, ASXL1 is also under expressed, but from 5-6%.
Lets skip the remaining blast cells as they appear for the most part to be related to diseases unrelated to flu or ULs. But lets make a table of the clast and blast cells with their respective protein type of clast or blast, and add the mean and fold change values for these genes from the UL and flu immuzined data for 1 and 7 days.
blastList <- blastSumms$gene
clastList <- clastSumms$geneblast_UL_df <- subset(UL, UL$Gene.Symbol %in% blastList)
blast_nonUL_df <- subset(nonUL, nonUL$Gene.Symbol %in% blastList)
clast_UL_df <- subset(UL, UL$Gene.Symbol %in% clastList)
clast_nonUL_df <- subset(nonUL, nonUL$Gene.Symbol %in% clastList)blast_UL_df_2 <- blast_UL_df %>% group_by(Gene.Symbol) %>% summarise_at(vars('GSM9093':'GSM9097'),mean)
blast_nonUL_df_2 <- blast_nonUL_df %>% group_by(Gene.Symbol) %>% summarise_at(vars('GSM9098':'GSM9102'),mean)
clast_UL_df_2 <- clast_UL_df %>% group_by(Gene.Symbol) %>% summarise_at(vars('GSM9093':'GSM9097'),mean)
clast_nonUL_df_2 <- clast_nonUL_df %>% group_by(Gene.Symbol) %>% summarise_at(vars('GSM9098':'GSM9102'),mean)blast_UL_df_2$mean <- apply(blast_UL_df_2[,2:6], 1, mean)
blast_nonUL_df_2$mean <- apply(blast_nonUL_df_2[,2:6],1,mean)
clast_UL_df_2$mean <- apply(clast_UL_df_2[,2:6],1,mean)
clast_nonUL_df_2$mean <- apply(clast_nonUL_df_2[,2:6],1,mean)colnames(blast_UL_df_2) <- c('gene','UL_1','UL_2','UL_3','UL_4','UL_5','UL_mean')
colnames(blast_nonUL_df_2) <- c('gene','nonUL_1','nonUL_2','nonUL_3','nonUL_4','nonUL_5','nonUL_mean')
colnames(clast_UL_df_2) <- c('gene','UL_1','UL_2','UL_3','UL_4','UL_5','UL_mean')
colnames(clast_nonUL_df_2) <- c('gene','nonUL_1','nonUL_2','nonUL_3','nonUL_4','nonUL_5','nonUL_mean')blast_UL_df_3 <- merge(blast_UL_df_2, blast_nonUL_df_2, by.x='gene',
by.y='gene')
blast_UL_df_4 <- blast_UL_df_3[,c(1,2:6,8:12,7,13)]
blast_UL_df_4$UL_foldchange <- blast_UL_df_3$UL_mean/blast_UL_df_3$nonUL_mean
colnames(blast_UL_df_4)## [1] "gene" "UL_1" "UL_2" "UL_3"
## [5] "UL_4" "UL_5" "nonUL_1" "nonUL_2"
## [9] "nonUL_3" "nonUL_4" "nonUL_5" "UL_mean"
## [13] "nonUL_mean" "UL_foldchange"clast_UL_df_3 <- merge(clast_UL_df_2, clast_nonUL_df_2, by.x='gene',by.y='gene')
clast_UL_df_4 <- clast_UL_df_3[,c(1,2:6,8:12,7,13)]
clast_UL_df_4$UL_foldchange <- clast_UL_df_4$UL_mean/clast_UL_df_4$nonUL_mean
colnames(clast_UL_df_4)## [1] "gene" "UL_1" "UL_2" "UL_3"
## [5] "UL_4" "UL_5" "nonUL_1" "nonUL_2"
## [9] "nonUL_3" "nonUL_4" "nonUL_5" "UL_mean"
## [13] "nonUL_mean" "UL_foldchange"row.names(clast_UL_df_4) <- NULL
row.names(blast_UL_df_4) <- NULL
clastBlast <- rbind(clast_UL_df_4,blast_UL_df_4)
head(clastBlast, 10)## gene UL_1 UL_2 UL_3 UL_4 UL_5 nonUL_1 nonUL_2
## 1 ACP5 73.3000 127.00 77.4000 105.500 110.5000 139.30 80.8000
## 2 CTSK 2524.5000 922.80 732.9000 1272.000 1201.2000 1377.00 973.1000
## 3 IGF1 1777.6000 836.40 418.0250 1210.975 1334.0000 410.05 1311.8500
## 4 IGFBP2 2224.7000 352.90 182.6000 417.400 429.1000 104.40 1005.7000
## 5 IGFBP5 873.8800 1161.90 1364.3200 1461.660 1732.3000 431.64 1161.8800
## 6 ABL1 594.9000 458.50 425.4000 461.600 354.1000 551.10 928.6000
## 7 ASXL1 140.8333 155.80 156.1333 131.300 143.5333 198.40 170.4667
## 8 BCR 75.9500 80.45 64.8000 74.450 93.3000 102.40 94.2000
## 9 CBFB 291.0000 176.45 212.8000 199.650 168.1500 250.50 334.9000
## 10 CEBPA 69.1000 109.50 86.9000 87.500 68.0000 60.00 27.3000
## nonUL_3 nonUL_4 nonUL_5 UL_mean nonUL_mean UL_foldchange
## 1 71.1000 100.1000 86.8000 98.740 95.6200 1.0326292
## 2 1080.4000 1093.1000 808.9000 1330.680 1066.5000 1.2477075
## 3 1063.7000 653.9250 730.4500 1115.400 833.9950 1.3374181
## 4 1024.0000 1189.2000 726.9000 721.340 810.0400 0.8904992
## 5 1166.2800 499.0400 476.8400 1318.812 747.1360 1.7651565
## 6 689.7000 471.5000 575.4000 458.900 643.2600 0.7133974
## 7 146.9333 160.1333 152.8333 145.520 165.7533 0.8779311
## 8 72.5500 84.1500 93.7500 77.790 89.4100 0.8700369
## 9 242.4500 276.2000 267.6000 209.610 274.3300 0.7640798
## 10 33.3000 40.4000 49.2000 84.200 42.0400 2.0028544clastBlastSumm <- rbind(blastSumms,clastSumms)
clastBlast_DF <- merge(clastBlastSumm,clastBlast, by.x='gene', by.y='gene')
clastBlast_DF## gene proteinSearched
## 1 ABL1 blast
## 2 ACP5 clast
## 3 ASXL1 blast
## 4 BCR blast
## 5 CBFB blast
## 6 CEBPA blast
## 7 CSF3 blast
## 8 CTSK clast
## 9 DNMT3A blast
## 10 ETV6 blast
## 11 FLT3 blast
## 12 GATA1 blast
## 13 GATA2 blast
## 14 HRAS blast
## 15 IGF1 clast
## 16 IGFBP2 clast
## 17 IGFBP5 clast
## 18 JAK2 blast
## 19 KIT blast
## 20 KMT2A blast
## 21 KRAS blast
## 22 MECOM blast
## 23 MYB blast
## 24 NPM1 blast
## 25 NRAS blast
## 26 SETBP1 blast
## 27 TP53 blast
## 28 U2AF1 blast
## EntrezSummary
## 1 This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]
## 2 This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]
## 3 This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
## 4 A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020]
## 5 The protein encoded by this gene is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2). The beta subunit is a non-DNA binding regulatory subunit; it allosterically enhances DNA binding by alpha subunit as the complex binds to the core site of various enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers and GM-CSF promoters. Alternative splicing generates two mRNA variants, each encoding a distinct carboxyl terminus. In some cases, a pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript consisting of the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain 11. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
## 6 This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain and recognizes the CCAAT motif in the promoters of target genes. The encoded protein functions in homodimers and also heterodimers with CCAAT/enhancer-binding proteins beta and gamma. Activity of this protein can modulate the expression of genes involved in cell cycle regulation as well as in body weight homeostasis. Mutation of this gene is associated with acute myeloid leukemia. The use of alternative in-frame non-AUG (GUG) and AUG start codons results in protein isoforms with different lengths. Differential translation initiation is mediated by an out-of-frame, upstream open reading frame which is located between the GUG and the first AUG start codons. [provided by RefSeq, Dec 2013]
## 7 This gene encodes a member of the IL-6 superfamily of cytokines. The encoded cytokine controls the production, differentiation, and function of granulocytes. Granulocytes are a type of white blood cell that are part of the innate immune response. A modified form of this protein is commonly administered to manage chemotherapy-induced neutropenia. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2020]
## 8 The protein encoded by this gene is a lysosomal cysteine proteinase involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is predominantly expressed in osteoclasts. However, the encoded protein is also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature. [provided by RefSeq, Apr 2013]
## 9 CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]
## 10 This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]
## 11 This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]
## 12 This gene encodes a protein which belongs to the GATA family of transcription factors. The protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and thrombocytopenia. [provided by RefSeq, Jul 2008]
## 13 This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]
## 14 This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]
## 15 The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]
## 16 The protein encoded by this gene is one of six similar proteins that bind insulin-like growth factors I and II (IGF-I and IGF-II). The encoded protein can be secreted into the bloodstream, where it binds IGF-I and IGF-II with high affinity, or it can remain intracellular, interacting with many different ligands. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the patient. Several transcript variants, one encoding a secreted isoform and the others encoding nonsecreted isoforms, have been found for this gene. [provided by RefSeq, Sep 2015]
## 17 IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3.
## 18 This gene product is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constituitively associated with the prolactin receptor and is required for responses to gamma interferon. Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis. [provided by RefSeq, Jul 2008]
## 19 This gene encodes a receptor tyrosine kinase. This gene was initially identified as a homolog of the feline sarcoma viral oncogene v-kit and is often referred to as proto-oncogene c-Kit. The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. This protein can be a membrane-bound or soluble protein. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]
## 20 This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]
## 21 This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
## 22 The protein encoded by this gene is a transcriptional regulator and oncoprotein that may be involved in hematopoiesis, apoptosis, development, and cell differentiation and proliferation. The encoded protein can interact with CTBP1, SMAD3, CREBBP, KAT2B, MAPK8, and MAPK9. This gene can undergo translocation with the AML1 gene, resulting in overexpression of this gene and the onset of leukemia. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
## 23 This gene encodes a protein with three HTH DNA-binding domains that functions as a transcription regulator. This protein plays an essential role in the regulation of hematopoiesis. This gene may be aberrently expressed or rearranged or undergo translocation in leukemias and lymphomas, and is considered to be an oncogene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
## 24 The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified. [provided by RefSeq, Aug 2017]
## 25 This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011]
## 26 This gene encodes a protein which contains a several motifs including a ski homology region and a SET-binding region in addition to three nuclear localization signals. The encoded protein has been shown to bind the SET nuclear oncogene which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
## 27 This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]
## 28 This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
## GeneCardsSummary
## 1 ABL1 (ABL Proto-Oncogene 1, Non-Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with ABL1 include Congenital Heart Defects And Skeletal Malformations Syndrome and Leukemia, Chronic Myeloid. Among its related pathways are ATM Pathway and Development Slit-Robo signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is ABL2.
## 2 ACP5 (Acid Phosphatase 5, Tartrate Resistant) is a Protein Coding gene. Diseases associated with ACP5 include Spondyloenchondrodysplasia With Immune Dysregulation and Spondyloenchondrodysplasia. Among its related pathways are Lysosome and ATP/ITP metabolism. Gene Ontology (GO) annotations related to this gene include hydrolase activity and ferric iron binding.
## 3 ASXL1 (ASXL Transcriptional Regulator 1) is a Protein Coding gene. Diseases associated with ASXL1 include Bohring-Opitz Syndrome and Myelodysplastic Syndrome. Among its related pathways are Metabolism of proteins and Regulation of activated PAK-2p34 by proteasome mediated degradation. Gene Ontology (GO) annotations related to this gene include transcription coactivator activity and retinoic acid receptor binding. An important paralog of this gene is ASXL3.
## 4 BCR (BCR Activator Of RhoGEF And GTPase) is a Protein Coding gene. Diseases associated with BCR include Leukemia, Chronic Myeloid and Leukemia, Acute Lymphoblastic 3. Among its related pathways are Ponatinib Pathway, Pharmacokinetics/Pharmacodynamics and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein tyrosine kinase activity and enzyme binding. An important paralog of this gene is ABR.
## 5 CBFB (Core-Binding Factor Subunit Beta) is a Protein Coding gene. Diseases associated with CBFB include Acute Myeloid Leukemia With Abnormal Bone Marrow Eosinophils Inv(16)(P13q22) Or T(16;16)(P13;Q22) and Leukemia, Acute Myeloid. Among its related pathways are Dual hijack model of Vif in HIV infection and Regulation of nuclear SMAD2/3 signaling. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription coactivator activity.
## 6 CEBPA (CCAAT Enhancer Binding Protein Alpha) is a Protein Coding gene. Diseases associated with CEBPA include Leukemia, Acute Myeloid and Acute Myeloid Leukemia With T(8;21)(Q22;Q22) Translocation. Among its related pathways are Transcriptional misregulation in cancer and E2F transcription factor network. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is CEBPE.
## 7 CSF3 (Colony Stimulating Factor 3) is a Protein Coding gene. Diseases associated with CSF3 include Neutropenia and Mucositis. Among its related pathways are PEDF Induced Signaling and Hematopoietic cell lineage. Gene Ontology (GO) annotations related to this gene include enzyme binding and growth factor activity.
## 8 CTSK (Cathepsin K) is a Protein Coding gene. Diseases associated with CTSK include Pycnodysostosis and Periodontitis. Among its related pathways are Lysosome and Degradation of the extracellular matrix. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and collagen binding. An important paralog of this gene is CTSS.
## 9 DNMT3A (DNA Methyltransferase 3 Alpha) is a Protein Coding gene. Diseases associated with DNMT3A include Tatton-Brown-Rahman Syndrome and Heyn-Sproul-Jackson Syndrome. Among its related pathways are One carbon pool by folate and Validated targets of C-MYC transcriptional repression. Gene Ontology (GO) annotations related to this gene include identical protein binding and methyltransferase activity. An important paralog of this gene is DNMT3B.
## 10 ETV6 (ETS Variant Transcription Factor 6) is a Protein Coding gene. Diseases associated with ETV6 include Thrombocytopenia 5 and Hematologic Cancer. Among its related pathways are Transcriptional misregulation in cancer and Diurnally Regulated Genes with Circadian Orthologs. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is ETV7.
## 11 FLT3 (Fms Related Receptor Tyrosine Kinase 3) is a Protein Coding gene. Diseases associated with FLT3 include Leukemia, Acute Myeloid and Acute Myeloblastic Leukemia Without Maturation. Among its related pathways are Transcriptional misregulation in cancer and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is PDGFRA.
## 12 GATA1 (GATA Binding Protein 1) is a Protein Coding gene. Diseases associated with GATA1 include Thrombocytopenia With Beta-Thalassemia, X-Linked and Thrombocytopenia, X-Linked, With Or Without Dyserythropoietic Anemia. Among its related pathways are C-MYB transcription factor network and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is GATA2.
## 13 GATA2 (GATA Binding Protein 2) is a Protein Coding gene. Diseases associated with GATA2 include Immunodeficiency 21 and Myelodysplastic Syndrome. Among its related pathways are Preimplantation Embryo and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is GATA3.
## 14 HRAS (HRas Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with HRAS include Costello Syndrome and Schimmelpenning-Feuerstein-Mims Syndrome. Among its related pathways are Negative regulation of MAPK pathway and GDNF-Family Ligands and Receptor Interactions. Gene Ontology (GO) annotations related to this gene include GTP binding and protein C-terminus binding. An important paralog of this gene is KRAS.
## 15 IGF1 (Insulin Like Growth Factor 1) is a Protein Coding gene. Diseases associated with IGF1 include Insulin-Like Growth Factor I and Pituitary Gland Disease. Among its related pathways are Apoptosis Modulation and Signaling and Transcriptional misregulation in cancer. Gene Ontology (GO) annotations related to this gene include growth factor activity and integrin binding. An important paralog of this gene is IGF2.
## 16 IGFBP2 (Insulin Like Growth Factor Binding Protein 2) is a Protein Coding gene. Diseases associated with IGFBP2 include Malignant Ovarian Cyst and Insulin-Like Growth Factor I. Among its related pathways are Hematopoietic Stem Cells and Lineage-specific Markers and Myometrial Relaxation and Contraction Pathways. Gene Ontology (GO) annotations related to this gene include insulin-like growth factor binding and insulin-like growth factor II binding. An important paralog of this gene is IGFBP4.
## 17 IGFBP5 (Insulin Like Growth Factor Binding Protein 5) is a Protein Coding gene. Diseases associated with IGFBP5 include Insulin-Like Growth Factor I and Renal Osteodystrophy. Among its related pathways are Myometrial Relaxation and Contraction Pathways and Senescence and Autophagy in Cancer. Gene Ontology (GO) annotations related to this gene include fibronectin binding and insulin-like growth factor I binding. An important paralog of this gene is IGFBP3.
## 18 JAK2 (Janus Kinase 2) is a Protein Coding gene. Diseases associated with JAK2 include Polycythemia Vera and Thrombocythemia 3. Among its related pathways are Negative regulation of MAPK pathway and RET signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is JAK3.
## 19 KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with KIT include Gastrointestinal Stromal Tumor and Piebald Trait. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is CSF1R.
## 20 KMT2A (Lysine Methyltransferase 2A) is a Protein Coding gene. Diseases associated with KMT2A include Wiedemann-Steiner Syndrome and Acute Myeloid Leukemia With T(9;11)(P22;Q23). Among its related pathways are Transcriptional misregulation in cancer and Lysine degradation. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and identical protein binding. An important paralog of this gene is KMT2B.
## 21 KRAS (KRAS Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with KRAS include Oculoectodermal Syndrome and Noonan Syndrome 3. Among its related pathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and Negative regulation of MAPK pathway. Gene Ontology (GO) annotations related to this gene include GTP binding. An important paralog of this gene is NRAS.
## 22 MECOM (MDS1 And EVI1 Complex Locus) is a Protein Coding gene. Diseases associated with MECOM include Radioulnar Synostosis With Amegakaryocytic Thrombocytopenia 2 and Acute Myeloid Leukemia With Inv3(P21;Q26.2) Or T(3;3)(P21;Q26.2). Among its related pathways are PKMTs methylate histone lysines and Chromatin organization. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and protein homodimerization activity. An important paralog of this gene is PRDM16.
## 23 MYB (MYB Proto-Oncogene, Transcription Factor) is a Protein Coding gene. Diseases associated with MYB include Angiocentric Glioma and Acute Basophilic Leukemia. Among its related pathways are C-MYB transcription factor network and Neural Crest Differentiation. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is MYBL1.
## 24 NPM1 (Nucleophosmin 1) is a Protein Coding gene. Diseases associated with NPM1 include Lymphomatoid Papulosis and Leukemia, Acute Myeloid. Among its related pathways are Development HGF signaling pathway and Tyrosine Kinases / Adaptors. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and protein homodimerization activity. An important paralog of this gene is NPM2.
## 25 NRAS (NRAS Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with NRAS include Ras-Associated Autoimmune Leukoproliferative Disorder and Melanocytic Nevus Syndrome, Congenital. Among its related pathways are Negative regulation of MAPK pathway and NGF Pathway. Gene Ontology (GO) annotations related to this gene include GTP binding. An important paralog of this gene is KRAS.
## 26 SETBP1 (SET Binding Protein 1) is a Protein Coding gene. Diseases associated with SETBP1 include Schinzel-Giedion Midface Retraction Syndrome and Mental Retardation, Autosomal Dominant 29. Among its related pathways are PKMTs methylate histone lysines. An important paralog of this gene is ASH1L.
## 27 TP53 (Tumor Protein P53) is a Protein Coding gene. Diseases associated with TP53 include Li-Fraumeni Syndrome and Osteogenic Sarcoma. Among its related pathways are Apoptosis Modulation and Signaling and Regulation of TP53 Activity through Acetylation. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is TP63.
## 28 U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) is a Protein Coding gene. Diseases associated with U2AF1 include Myelodysplastic Syndrome and Myeloid Leukemia. Among its related pathways are Cleavage of Growing Transcript in the Termination Region and Transport of Mature Transcript to Cytoplasm. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and nucleotide binding. An important paralog of this gene is U2AF1L5.
## UniProtKB_Summary
## 1 Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner. Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity).\n ABL1_HUMAN,P00519\n
## 2 Involved in osteopontin/bone sialoprotein dephosphorylation. Its expression seems to increase in certain pathological states such as Gaucher and Hodgkin diseases, the hairy cell, the B-cell, and the T-cell leukemias.\n PPA5_HUMAN,P13686\n
## 3 Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG) (PubMed:16606617). Acts as coactivator of RARA and RXRA through association with NCOA1 (PubMed:16606617). Acts as corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity (By similarity). Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (PubMed:20436459). Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing (PubMed:30982744).\n ASXL1_HUMAN,Q8IXJ9\n
## 4 Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:7479768, PubMed:1903516, PubMed:17116687). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:7479768, PubMed:23940119). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119).\n BCR_HUMAN,P11274\n
## 5 Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation.\n PEBB_HUMAN,Q13951\n
## 6 Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes (PubMed:11242107). During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). Critical for the proper development of the liver and the lung (By similarity). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (By similarity). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Downregulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters. Proliferation arrest also depends on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity).\n CEBPA_HUMAN,P49715\n
## 7 Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes.\n CSF3_HUMAN,P09919\n
## 8 Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (PubMed:11082042).\n CATK_HUMAN,P43235\n
## 9 Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity.\n DNM3A_HUMAN,Q9Y6K1\n
## 10 Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation.\n ETV6_HUMAN,P41212\n
## 11 Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.\n FLT3_HUMAN,P36888\n
## 12 Transcriptional activator or repressor which probably serves as a general switch factor for erythroid development. It binds to DNA sites with the consensus sequence 5'-[AT]GATA[AG]-3' within regulatory regions of globin genes and of other genes expressed in erythroid cells. Activates the transcription of genes involved in erythroid differentiation of K562 erythroleukemia cells, including HBB, HBG1/2, ALAS2 and HMBS (PubMed:24245781).\n GATA1_HUMAN,P15976\n
## 13 Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'-AGATAG-3'.\n GATA2_HUMAN,P23769\n
## 14 Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151).\n RASH_HUMAN,P01112\n
## 15 The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity). Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiatiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:19578119, PubMed:22351760, PubMed:23696648, PubMed:23243309).\n IGF1_HUMAN,P05019\n
## 16 Inhibits IGF-mediated growth and developmental rates. IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.\n IBP2_HUMAN,P18065\n
## 17 IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.\n IBP5_HUMAN,P24593\n
## 18 Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:7615558). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980).\n JAK2_HUMAN,O60674\n
## 19 Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.\n KIT_HUMAN,P10721\n
## 20 Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation (PubMed:12453419, PubMed:20677832, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-induced apoptosis. Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer. Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity).\n KMT2A_HUMAN,Q03164\n
## 21 Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the regulation of cell proliferation (PubMed:23698361, PubMed:22711838). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306).\n RASK_HUMAN,P01116\n
## 22 [Isoform 1]: Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis.\n MECOM_HUMAN,Q03112\n
## 23 Transcriptional activator; DNA-binding protein that specifically recognize the sequence 5'-YAAC[GT]G-3'. Plays an important role in the control of proliferation and differentiation of hematopoietic progenitor cells.\n MYB_HUMAN,P10242\n
## 24 Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029).\n NPM_HUMAN,P06748\n
## 25 Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.\n RASN_HUMAN,P01111\n
## 26 no summary
## 27 Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492).\n P53_HUMAN,P04637\n
## 28 Plays a critical role in both constitutive and enhancer-dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for accurate 3'-splice site selection. Recruits U2 snRNP to the branch point. Directly mediates interactions between U2AF2 and proteins bound to the enhancers and thus may function as a bridge between U2AF2 and the enhancer complex to recruit it to the adjacent intron.\n U2AF1_HUMAN,Q01081\n
## todaysDate UL_1 UL_2 UL_3 UL_4
## 1 Wed Aug 05 08:55:09 2020 594.90000 458.50000 425.40000 461.60000
## 2 Wed Aug 05 07:15:44 2020 73.30000 127.00000 77.40000 105.50000
## 3 Wed Aug 05 08:55:19 2020 140.83333 155.80000 156.13333 131.30000
## 4 Wed Aug 05 08:55:24 2020 75.95000 80.45000 64.80000 74.45000
## 5 Wed Aug 05 08:55:32 2020 291.00000 176.45000 212.80000 199.65000
## 6 Wed Aug 05 08:55:27 2020 69.10000 109.50000 86.90000 87.50000
## 7 Wed Aug 05 08:55:33 2020 3.70000 13.40000 5.50000 4.80000
## 8 Wed Aug 05 07:15:43 2020 2524.50000 922.80000 732.90000 1272.00000
## 9 Wed Aug 05 08:55:30 2020 4.70000 5.10000 28.30000 10.50000
## 10 Wed Aug 05 08:55:17 2020 53.90000 31.70000 29.30000 26.50000
## 11 Wed Aug 05 08:55:00 2020 5.40000 9.60000 30.70000 35.60000
## 12 Wed Aug 05 08:55:16 2020 17.40000 53.20000 29.10000 54.30000
## 13 Wed Aug 05 08:55:21 2020 40.83333 93.96667 87.86667 76.03333
## 14 Wed Aug 05 08:55:42 2020 195.50000 88.60000 136.10000 107.30000
## 15 Wed Aug 05 07:15:45 2020 1777.60000 836.40000 418.02500 1210.97500
## 16 Wed Aug 05 07:15:48 2020 2224.70000 352.90000 182.60000 417.40000
## 17 Wed Aug 05 07:15:50 2020 873.88000 1161.90000 1364.32000 1461.66000
## 18 Wed Aug 05 08:55:03 2020 36.25000 33.75000 48.05000 33.75000
## 19 Wed Aug 05 08:55:01 2020 66.20000 89.10000 84.20000 34.40000
## 20 Wed Aug 05 08:55:25 2020 93.10000 154.70000 180.34000 123.44000
## 21 Wed Aug 05 08:55:22 2020 108.60000 290.16667 232.60000 162.60000
## 22 Wed Aug 05 08:55:28 2020 16.66667 36.06667 33.53333 39.96667
## 23 Wed Aug 05 08:55:31 2020 5.95000 7.20000 12.20000 25.90000
## 24 Wed Aug 05 08:55:07 2020 1873.70000 1490.93333 2129.36667 1311.43333
## 25 Wed Aug 05 08:55:39 2020 109.40000 54.80000 39.40000 43.70000
## 26 Wed Aug 05 08:55:20 2020 218.80000 273.80000 267.90000 311.50000
## 27 Wed Aug 05 08:55:23 2020 114.30000 120.90000 78.70000 93.45000
## 28 Wed Aug 05 08:55:26 2020 416.30000 643.70000 560.10000 452.10000
## UL_5 nonUL_1 nonUL_2 nonUL_3 nonUL_4 nonUL_5 UL_mean
## 1 354.10000 551.10000 928.6000 689.7000 471.50000 575.4000 458.90000
## 2 110.50000 139.30000 80.8000 71.1000 100.10000 86.8000 98.74000
## 3 143.53333 198.40000 170.4667 146.9333 160.13333 152.8333 145.52000
## 4 93.30000 102.40000 94.2000 72.5500 84.15000 93.7500 77.79000
## 5 168.15000 250.50000 334.9000 242.4500 276.20000 267.6000 209.61000
## 6 68.00000 60.00000 27.3000 33.3000 40.40000 49.2000 84.20000
## 7 9.30000 119.60000 8.6000 4.0000 6.20000 4.6000 7.34000
## 8 1201.20000 1377.00000 973.1000 1080.4000 1093.10000 808.9000 1330.68000
## 9 24.80000 24.50000 6.8000 6.5000 42.50000 35.3000 14.68000
## 10 52.20000 34.20000 27.6000 39.6000 25.30000 48.5000 38.72000
## 11 34.20000 23.70000 5.7000 28.8000 36.40000 35.0000 23.10000
## 12 8.60000 11.40000 4.4000 6.5000 9.30000 20.5000 32.52000
## 13 95.66667 148.63333 124.7333 115.7667 175.13333 142.5667 78.87333
## 14 140.40000 99.80000 123.7000 117.3000 142.90000 133.2000 133.58000
## 15 1334.00000 410.05000 1311.8500 1063.7000 653.92500 730.4500 1115.40000
## 16 429.10000 104.40000 1005.7000 1024.0000 1189.20000 726.9000 721.34000
## 17 1732.30000 431.64000 1161.8800 1166.2800 499.04000 476.8400 1318.81200
## 18 35.40000 62.55000 70.9000 58.7000 52.25000 52.8500 37.44000
## 19 68.60000 119.40000 282.6000 102.4000 124.40000 227.5000 68.50000
## 20 134.46000 128.64000 104.6400 102.2000 134.14000 136.5600 137.20800
## 21 178.73333 129.50000 130.2333 145.5667 110.33333 136.1000 194.54000
## 22 36.90000 47.06667 46.7000 28.1000 63.36667 54.3000 32.62667
## 23 18.40000 13.50000 4.8500 1.5000 18.35000 17.5500 13.93000
## 24 1263.76667 1706.76667 1583.7000 1363.3667 1428.43333 1194.4667 1613.84000
## 25 56.60000 74.40000 107.0000 65.9000 59.00000 62.5000 60.78000
## 26 205.80000 196.80000 223.7000 266.3000 224.90000 195.1000 255.56000
## 27 80.25000 91.75000 48.6500 78.7500 77.20000 74.6000 97.52000
## 28 442.00000 498.30000 541.2000 467.2000 501.40000 431.6000 502.84000
## nonUL_mean UL_foldchange
## 1 643.26000 0.7133974
## 2 95.62000 1.0326292
## 3 165.75333 0.8779311
## 4 89.41000 0.8700369
## 5 274.33000 0.7640798
## 6 42.04000 2.0028544
## 7 28.60000 0.2566434
## 8 1066.50000 1.2477075
## 9 23.12000 0.6349481
## 10 35.04000 1.1050228
## 11 25.92000 0.8912037
## 12 10.42000 3.1209213
## 13 141.36667 0.5579344
## 14 123.38000 1.0826714
## 15 833.99500 1.3374181
## 16 810.04000 0.8904992
## 17 747.13600 1.7651565
## 18 59.45000 0.6297729
## 19 171.26000 0.3999766
## 20 121.23600 1.1317430
## 21 130.34667 1.4924816
## 22 47.90667 0.6810465
## 23 11.15000 1.2493274
## 24 1455.34667 1.1089042
## 25 73.76000 0.8240239
## 26 221.36000 1.1544995
## 27 74.19000 1.3144629
## 28 487.94000 1.0305365write.csv(clastBlast_DF,'clastBlastSumm.csv',row.names=FALSE)Lets make the flu immunization data tables now.
clastFlu1 <- subset(FluImz_1day, FluImz_1day$Gene.Symbol %in% clastList)
clastFlu7 <- subset(FluImz_7day, FluImz_7day$Gene.Symbol %in% clastList)
blastFlu1 <- subset(FluImz_1day, FluImz_1day$Gene.Symbol %in% blastList)
blastFlu7 <- subset(FluImz_7day, FluImz_7day$Gene.Symbol %in% blastList)
nonImzHealthy_clast <- subset(healthy_noFluImz, healthy_noFluImz$Gene.Symbol %in%
clastList)
nonImzHealthy_blast <- subset(healthy_noFluImz, healthy_noFluImz$Gene.Symbol %in%
blastList)
nonImz_blastClast <- rbind(nonImzHealthy_blast,nonImzHealthy_clast)
flu1_blastClast <- rbind(blastFlu1,clastFlu1)
flu7_blastClast <- rbind(blastFlu7, clastFlu7)nonImz_blastClast_2 <- nonImz_blastClast %>% group_by(Gene.Symbol) %>%
summarise_at(vars('Flu.non.immunized.healthy':'Flu.non.immunized.healthy.5'),mean)
flu1_blastClast_2 <- flu1_blastClast %>% group_by(Gene.Symbol) %>%
summarise_at(vars('Flu.Immunized.Only.Day.1':'Flu.Immunized.Only.Day.1.2'),mean)
flu7_blastClast_2 <- flu7_blastClast %>% group_by(Gene.Symbol) %>%
summarise_at(vars('Flu.Immunized.Only.Day.7':'Flu.Immunized.Only.Day.7.2'),mean)nonImz_blastClast_2$nonImmz_mean <- apply(nonImz_blastClast_2[,2:7],1,mean)
flu1_blastClast_2$fluImz_1day_mean <- apply(flu1_blastClast_2[2:4],1,mean)
flu7_blastClast_2$fluImz_7day_mean <- apply(flu7_blastClast_2[2:4],1,mean)flu7_blastClast_3 <- merge(nonImz_blastClast_2,flu7_blastClast_2, by.x='Gene.Symbol',
by.y='Gene.Symbol')
FLU_blastClast <- merge(flu7_blastClast_3,flu1_blastClast_2, by.x='Gene.Symbol',
by.y='Gene.Symbol')FLU_blastClast2 <- FLU_blastClast[,c(1:7,9:11,13:15,8,12,16)]
FLU_blastClast2$Flu1_foldchange <- FLU_blastClast2$fluImz_1day_mean/FLU_blastClast2$nonImmz_mean
FLU_blastClast2$Flu7_foldchange <- FLU_blastClast2$fluImz_7day_mean/FLU_blastClast2$nonImmz_mean
colnames(FLU_blastClast2)[1] <- 'gene'
colnames(FLU_blastClast2)## [1] "gene" "Flu.non.immunized.healthy"
## [3] "Flu.non.immunized.healthy.1" "Flu.non.immunized.healthy.2"
## [5] "Flu.non.immunized.healthy.3" "Flu.non.immunized.healthy.4"
## [7] "Flu.non.immunized.healthy.5" "Flu.Immunized.Only.Day.7"
## [9] "Flu.Immunized.Only.Day.7.1" "Flu.Immunized.Only.Day.7.2"
## [11] "Flu.Immunized.Only.Day.1" "Flu.Immunized.Only.Day.1.1"
## [13] "Flu.Immunized.Only.Day.1.2" "nonImmz_mean"
## [15] "fluImz_7day_mean" "fluImz_1day_mean"
## [17] "Flu1_foldchange" "Flu7_foldchange"FLU_blastClast3 <- merge(clastBlastSumm, FLU_blastClast2, by.x='gene', by.y='gene')
colnames(FLU_blastClast3) <- gsub('.Only.','',colnames(FLU_blastClast3))write.csv(FLU_blastClast3,'blastClast_Flu.csv', row.names=FALSE)Those tables will be used in Tableau to chart results and make it easier to interpret these genes in the blast and clast cells in uterine leiomyomas and in flu immunized samples.