1. Background / Goal

Reviewer request: examine BRCA1P1 patterns in BRCA1/2-mutant vs WT tumors across TCGA solid tumor datasets (breast, ovarian, prostate), and further stratify breast cancer by basal/TNBC subtype where possible.

This notebook runs two related analyses:

Part A: RNA expression (RPKM) for BRCA + OV

Part B: CNV (seg.mean log2 ratio) for BRCA + OV + PRAD

BRCA1P1 TCGA RNA EXpression

BRCA1P1 expression was quantified using the Ensembl/HAVANA pseudogene annotation RP11-242D8.2 and RP11-242D8.3(ENSG00000267595),

## Tumor patients with expression: 837 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       752
## 2 BRCA1/2 Mutant    42
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT                 0 0.228  0.493 0.926         1.95    752
## 2 BRCA1/2 Mutant             0 0.151  0.334 0.538         0.893    42

## BRCA basal/TNBC N: 128 
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT                 0 0.156  0.362 0.590         1.18    115
## 2 BRCA1/2 Mutant             0 0.168  0.447 0.542         0.709    13

## # A tibble: 2 × 7
##   Basal_status lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 Basal                    0 0.157  0.376 0.587          1.23   128
## 2 Other                    0 0.235  0.527 0.984          2.10   666

## Tumor patients with expression: 837 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       752
## 2 BRCA1/2 Mutant    42
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT            0      0.185  0.355 0.603         1.19    752
## 2 BRCA1/2 Mutant        0.0372 0.168  0.281 0.438         0.683    42

## BRCA basal/TNBC N: 128 
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT            0      0.146  0.255 0.440         0.834   115
## 2 BRCA1/2 Mutant        0.0372 0.218  0.327 0.500         0.890    13

## # A tibble: 2 × 7
##   Basal_status lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 Basal                    0 0.148  0.259 0.450         0.890   128
## 2 Other                    0 0.196  0.369 0.625         1.25    666

## Tumor patients with expression: 412 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       248
## 2 BRCA1/2 Mutant    21
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT                 0 0.182  0.411 0.683         1.41    248
## 2 BRCA1/2 Mutant             0 0.147  0.305 0.477         0.662    21

## BRCA patients with BRCA1 expression: 1064
## BRCA patients in BRCA1 plot table: 994
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       941
## 2 BRCA1/2 Mutant    53
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT              8.54  231.   354.  559.         1045.   941
## 2 BRCA1/2 Mutant         26.5   211.   320.  497.          886.    53

## BRCA basal/TNBC N (BRCA1 expr): 171
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT              8.54 247.    401.  575.         1063.   152
## 2 BRCA1/2 Mutant         26.5   99.3   216.  404.          719.    19

## # A tibble: 2 × 7
##   Basal_status lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 Basal                 8.54  200.   387.  572.         1119.   171
## 2 Other                11.3   231.   344.  548.         1015.   823

## OV patients with BRCA1 expression: 201
## OV patients in BRCA1 plot table: 201
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       185
## 2 BRCA1/2 Mutant    16
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT              5.50 132.    223.  312.          527.   185
## 2 BRCA1/2 Mutant         18.6   62.9   115.  236.          372.    16

## PRAD patients with BRCA1 expression: 488
## PRAD patients in BRCA1 plot table: 488
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       479
## 2 BRCA1/2 Mutant     9
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT              28.8  81.6   107.  142.          233.   479
## 2 BRCA1/2 Mutant          73.9 116.    210.  273.          273.     9

## Tumor patients with expression: 412 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       248
## 2 BRCA1/2 Mutant    21
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker    q1 median    q3 upper_whisker     n
##   <fct>                  <dbl> <dbl>  <dbl> <dbl>         <dbl> <int>
## 1 BRCA1/2 WT                 0 0.263  0.655 1.18           2.46   248
## 2 BRCA1/2 Mutant             0 0.121  0.315 0.662          1.36    21

## Total segments: 198581 
## Samples in CNV plot table: 994 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       941
## 2 BRCA1/2 Mutant    53
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker     q1  median     q3 upper_whisker     n
##   <fct>                  <dbl>  <dbl>   <dbl>  <dbl>         <dbl> <int>
## 1 BRCA1/2 WT            -0.647 -0.227 -0.0156 0.0628         0.487   941
## 2 BRCA1/2 Mutant        -0.600 -0.291 -0.119  0.0622         0.507    53
## # A tibble: 2 × 5
##   BRCA_group         n mean_segmean median_segmean sd_segmean
##   <fct>          <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA1/2 WT       941      -0.0574        -0.0156      0.267
## 2 BRCA1/2 Mutant    53      -0.0844        -0.119       0.306
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by BRCA_group
## W = 27088, p-value = 0.2902
## alternative hypothesis: true location shift is not equal to 0

## # A tibble: 2 × 7
##   subtype_group lower_whisker     q1  median      q3 upper_whisker     n
##   <fct>                 <dbl>  <dbl>   <dbl>   <dbl>         <dbl> <int>
## 1 BRCA_Basal           -0.621 -0.274 -0.150  -0.0183         0.215   171
## 2 Other                -0.647 -0.203 -0.0022  0.0947         0.529   772
## # A tibble: 2 × 5
##   subtype_group     n mean_segmean median_segmean sd_segmean
##   <fct>         <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA_Basal      171      -0.152         -0.150       0.206
## 2 Other           772      -0.0413        -0.0022      0.279
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by subtype_group
## W = 46606, p-value = 1.744e-09
## alternative hypothesis: true location shift is not equal to 0

## Total segments: 75613 
## Samples in CNV plot table: 489 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       480
## 2 BRCA1/2 Mutant     9
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker       q1 median     q3 upper_whisker     n
##   <fct>                  <dbl>    <dbl>  <dbl>  <dbl>         <dbl> <int>
## 1 BRCA1/2 WT           -0.0501 -0.00415 0.0088 0.0273        0.0725   480
## 2 BRCA1/2 Mutant       -0.0273  0.0071  0.0167 0.0437        0.0438     9
## # A tibble: 2 × 5
##   BRCA_group         n mean_segmean median_segmean sd_segmean
##   <fct>          <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA1/2 WT       480      -0.0223         0.0088      0.146
## 2 BRCA1/2 Mutant     9       0.0879         0.0167      0.215
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by BRCA_group
## W = 1578.5, p-value = 0.1666
## alternative hypothesis: true location shift is not equal to 0

## Total segments: 200978 
## Samples in CNV plot table: 398 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       365
## 2 BRCA1/2 Mutant    33
## # A tibble: 2 × 7
##   BRCA_group     lower_whisker     q1 median      q3 upper_whisker     n
##   <fct>                  <dbl>  <dbl>  <dbl>   <dbl>         <dbl> <int>
## 1 BRCA1/2 WT             -1.11 -0.540 -0.398 -0.130          0.480   365
## 2 BRCA1/2 Mutant         -1.17 -0.577 -0.475 -0.0272         0.519    33
## # A tibble: 2 × 5
##   BRCA_group         n mean_segmean median_segmean sd_segmean
##   <fct>          <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA1/2 WT       365       -0.346         -0.398      0.302
## 2 BRCA1/2 Mutant    33       -0.312         -0.475      0.371
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by BRCA_group
## W = 5979.5, p-value = 0.9465
## alternative hypothesis: true location shift is not equal to 0