When I give a list of genes regulated by my protein of interest as input in GSEA MSigDB, does the output of C3 TFT mean that my set of genes regulate these Transcription factors?
Dear Shilpa,
Gene-set enrichment analysis gives an estimate of how associated with a specific function/pathway/group of genes.
If you get C3 TFT as 'positively enriched' for your list of genes, then it means that your genes are more likely to be C3 TFT than by chance.
You also need to check the enrichment value: if it is negative then your list of genes is actually depleted regarding your genes set.
HTH,
Kevin
Dear Kevin... Thank you for the answer. But then whatever hits I get in C3 TFT should me a subset of genes from my input genes right? Coz many of the hits from the C3 TFT are not in the input genes I provided .
My understanding for GSEA is that you provide a list of all the genes you studied, ranked by whatever metrics you used (e.g., pvalue). Then, GSEA is done and return sets of genes for which the enrichment is significantly high. Therefore, it does not necessarily mean that it will only contain significant genes, but just that the ranking shows enrichment.
If I may complete the previous answers: GSEA calculate enrichment of a set of genes over the entire genome. If you get hits in C3 TFT, it means that your set of genes are probable targets of the transcription factors that are indicated by GSEA. Therefore if what you call "hits" are the C3 TFT results, it's understandable that they are not (all) in your gene subset. However, if you look at the genes which make the C3 TFT result significant, they should all be a subset of your gene list. Now, if your set of genes is regulated by a protein of interest and you get indication of putative regulation by some TF, it might be that your protein of interest is another TF working in dimer or a transcriptional cofactor and it may be worth investigating.
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