Obtain data

Comparing genes differentially expressed between young and old mice and rat. The raw data from rat bulk RNAseq has been downloaded from GEO at the accession GSE134765 (Neumann et al. 2019). The differential expression analysis between young and old rat was done following DESeq2 workflow (Love, Huber, and Anders 2014)

The mouse differential expression has been obtained from (Ximerakis et al. 2019), Supplementary Table 6: Differential gene expression data between young and old cell types, extracting only OPCs tab.The DGE techniques used here have more power to assign significance of subtle changes in highly transcribed genes.

Load R libraries

## Loading required package: grid
## Loading required package: futile.logger
## here() starts at C:/Users/nbestard/OneDrive/Laura

Load data

Compare size initial datasets

## [1] 12572
## [1] 15137
## [1] 10497

Before selecting for differentially expressed genes the datasets are of similar size, in total there are 10497 genes in common between both of them.

Filter for DE genes

The genes are selected on the basis of being differentially expressed with an adjusted p-value < 0.05

## [1] 4314
## [1] 445

The rat dataset has 4314 DE genes, and the mouse dataset 445

Compare both species

Find the downregulated genes in both species

Downregulated genes in old rat/mouse are the ones with a negative foldchange. It could be possible to be more strict about the amount of change (e.g. more than 10% change), but the filters have been kept quite flexible for the first filtering. See Src/rat_young_oldDE.Rmd for more details.

The 41 downregulated genes in both species are:

## [1] "Ccnb1, Cdc20, Cdca3, Cdk1, Cdkn2c, Cenpa, Cenpl, Cks2, Ctbp1, Dbn1, Dynll1, Emid1, Ezh2, Fabp7, Fbll1, Fyn, Gap43, Gp1bb, Hmgb2, Hmmr, Kif5a, Knstrn, Lhx2, Marcksl1, Ndn, Nrsn1, Pbk, Pcp4, Pfn2, Pllp, Prdx2, Racgap1, S100a16, Snrpn, Sox11, Spc24, Spc25, Ttc9b, Tuba1a, Ube2c, Ube2s"

Find the upregulated genes in both species

The upregulated ones in old rat/mouse have a positive foldchange.

The 11 upregulated genes in both species are:

## [1] "Apoe, C4b, Clasp2, Cp, Evi2a, Il33, Maf, Rpl23a, Rpl6, Skap2, Son"

Plot “MA” with genes differentially expressed in both species

These plots indicate the expression level ( mean counts) of selected genes plotted against the amount of change between young and old rats (log FC). The pvalues and FoldChange are extracted from the rat dataset Bear in mind the plot axis are at different scale.

Additional plots

Volcano plot

The pvalues and FoldChange are extracted from the rat dataset

Session information

Click to expand 
## R version 4.0.4 (2021-02-15)
## Platform: x86_64-w64-mingw32/x64 (64-bit)
## Running under: Windows 10 x64 (build 19041)
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## [5] LC_TIME=English_United Kingdom.1252    
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## attached base packages:
## [1] grid      stats     graphics  grDevices utils     datasets  methods  
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## other attached packages:
## [1] here_1.0.1          ggrepel_0.9.1       ggplot2_3.3.3      
## [4] VennDiagram_1.6.20  futile.logger_1.4.3
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## [34] farver_2.1.0         purrr_0.3.4          lambda.r_1.2.4      
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## [43] labeling_0.4.2       utf8_1.2.1           stringi_1.5.3       
## [46] munsell_0.5.0        crayon_1.4.1

Reference

Love, Michael I., Wolfgang Huber, and Simon Anders. 2014. “Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.” Genome Biology 15 (12): 550. https://doi.org/10.1186/s13059-014-0550-8.
Neumann, Björn, Roey Baror, Chao Zhao, Michael Segel, Sabine Dietmann, Khalil S. Rawji, Sarah Foerster, et al. 2019. “Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells.” Cell Stem Cell 25 (4): 473–485.e8. https://doi.org/10.1016/j.stem.2019.08.015.
Ximerakis, Methodios, Scott L. Lipnick, Brendan T. Innes, Sean K. Simmons, Xian Adiconis, Danielle Dionne, Brittany A. Mayweather, et al. 2019. “Single-cell transcriptomic profiling of the aging mouse brain.” Nature Neuroscience 22 (10): 1696–1708. https://doi.org/10.1038/s41593-019-0491-3.