z0on / GO_MWU

Rank-based Gene Ontology analysis of gene expression data
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Choice of ranking metric: qvalue, shrunk logFC #21

Closed mewojciechowski closed 3 months ago

mewojciechowski commented 3 months ago

Hi Mikhail,

Thank you for providing and maintaining the tool. I really appreciate it. I have a question regarding the ranking metric for running GO_MWU. Do you suggest using logFC or a qvalue with a sign added based on logfc as the ranking measure for the genes? Or maybe some more elaborate measure such as -log10(p-value) * log2(foldchange)? What's your current take on that.

Best wishes

Marek

z0on commented 3 months ago

Hi Marek - thanks for using my tool! I don’t recommend bringing any measure of significance into this, since it creates bias towards highly expressed genes. Even a tiny fold-change in them is significant because counts are so large. You basically get ribosomal proteins all the time in your GO summaries. Log-fc is a better one: it has its own problem of being noisy for low-expressed genes, but at least the direction of the noise is random so it should average out across all genes in a GO category. Misha

On Tue, May 7, 2024 at 3:25 AM mewojciechowski @.***> wrote:

Hi Mikhail,

Thank you for providing and maintaining the tool. I really appreciate it. I have a question regarding the ranking metric for running GO_MWU. Do you suggest using logFC or a qvalue with a sign added based on logfc as the ranking measure for the genes? Or maybe some more elaborate measure such as -log10(p-value) * log2(foldchange)? What's your current take on that.

Best wishes

Marek

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mewojciechowski commented 3 months ago

Hi Misha,

Thanks! Makes perfect sense.

Cheers

Marek