How to exclude sex-dependent genes from RNA-Seq?
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11 weeks ago
bxxxmxxxx ▴ 10

Hi all,

I am working on a RNASEQ dataset that includes mice brain samples from both healthy and disease- model male and female mice. The disease was induced using CRISPR and since we're testing the model, we want to see if there are sex dependent differences. One comment came up saying that the significant differences we see in the model are dependent on the sex genes (like XIST - an X inactivation gene that is only prevalent in females) and I was told to remove them from the gene_count file that I have. Does anyone have a list of genes that could be considered sex-dependent? Any tips on how to do this? I am new to DESEQ2 analysis of RNASEQ samples.

Thank you

RNA-seq DESeq2 • 432 views
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Just do a literature search, e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136152/, https://www.nature.com/articles/s41598-021-98059-9, etc. -- look at the supp. tables of sex-dependent genes, cite those papers, remove those genes, try your model on your new list of genes, and report those results somewhere in your paper as a response to your reviewer.

I assume that sex shouldn't make a different unless it's confounded with your disease condition.

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Will excluding X and Y chromosome genes not address this?

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It might work -- but a reviewer might come back and say that there are sex-dependent genes on autosomes (and even lncRNAs like Xist can regulate in trans). But this would probably be the easiest thing to try initially.

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