Is there any recommended RNAseq ranking for DEGs/driver genes

Question

[dew]

Dear guys,

May I know if there are any tools to rank the DEGs or calculate the cell differentiation driver genes' "effects/power" over time?

As the RNAseq results show that the treatment is so similar to the control, and the signal is rather weak, the difference between the treatment and the control is so small(very few DEGs number, high padj that most are close to 1, and only a few below 0.05).

So wondering how to test if the treatment effects are comprised by the strength of the cell differentiation. A score like a "polygenic risk score" for the cell differentiation markers? ...? Or maybe there are other ways to interpret this?

Thanks a lot!

[LChart]

The "score" at least seems doable if this is a well-studied differentiation. If you can define initial, terminal, and intermediate states from either a single-cell study, or a timecourse study that examined this particular differentiation, then you can do something like:

1. Compute a small number (<=100) of landmarks between the reference states
2. Summarize landmark expression into an expression vector
3. Compute the correlation of your observed expression to each of the landmarks (ideally this should be positive)

These relative correlations would basically be a "score" along the differentiation path; though it only really makes sense if there's not some huge batch effect that renders all of the correlations small or negative.

However, I'm not sure what you mean by the effect of a driver gene -- unless you are specifically over-expressing a single gene, I don't think there's a way to apportion any score among different genes; you can only measure total effect.

[dew]

Thanks a lot for the enlightenment! It's very valuable!

Will try to do the correlation of observed expression vs landmarks. The driver gene is trying to say the genes that lead the cells to differentiate, maybe it's indeed the landmarks, as the four markers in the stem cell keep the stemness.

Thank you very much!