Why does the same transcription factor have many regulons?

[M-jk22]

In the analysis results, I found that the same transcription factor might correspond to many target gene sets, each with its own AUC. So, can I understand that even the same TF can have many regulons, and that the TF activity in each cell is the result of processing these regulon scores?

[VincentGardeux]

Hi @M-jk22,

From what I understood these are not the regulons yet, but the modules that were computed on the adjacencies graph.
But then you have another step that summarizes this information at the TF level, thus creating one unique regulon per module.
I think you miss a step of the pipeline? It's like you've run the pruning step, but not the df2regulon step?

[M-jk22]

Hi @VincentGardeux,
Thank you for your reply. Yes, this is the result after running pyscenic ctx. I thought that during the analysis process, one transcription factor would correspond to a group of target genes. However, from the current analysis results, it seems that after computing with the adjacency graph, one transcription factor is associated with many modules. Then, these modules are integrated using pyscenic aucell to obtain the AUCell score for the transcription factor regulon. I'm not sure if my description is correct. What does the AUC value of each module represent then? Can we use the AUC to filter these modules to select target genes?

[VincentGardeux]

Hi @M-jk22,
I am not running the CLI tool, but the notebook version. I did not know that the pyscenic ctx was not returning the summarized regulons but instead the modules (I am no author of this tool, just a user).

There is a preprocessing step, before running the AUCell, where the modules are integrated into regulons, by concatenating all target genes of each module associated with a certain TF, and taking the top motif (higher NES). Then, the AUCell is computed on this summarized TF. So I assume that in the CLI version, the preprocessing is generated while running the AUCell step.

[M-jk22]

Hi @VincentGardeux,
Thanks for your reply! I've learned a lot from chatting with you. Wishing you a happy and joyful life!