supporting evidence for the regulate potential of a ligand on a target

[zhenzhenyang-psu]

Dear multinichenetr team, Thanks for developing such a wonderful tool! I have ran multinichenetr and identified a very interesting ligand for the downregulation of my target gene. I tried to find evidence that supports the downregulation of this ligand on my target using google search and pubmed, but could not find it. The ligand of my interest is CTHRC1 and running multinichenetr on my dataset it shows it could downregulate CLDN7. I am eager to find evidence that underpins this regulation. Could you first elaborate on how the regulate potential of a ligand on target genes is predicted? Also could you suggest ways in helping me find the relevant references or datasets for me to gain confidence on this regulation?

Thanks very much, and looking forward to your reply. Best, Zhenzhen

[browaeysrobin]

Hi @zhenzhenyang-psu

To check the underlying data sources and potential signaling paths between ligand and target gene, you can check the following vignette from the NicheNet pathway: https://github.com/saeyslab/nichenetr/blob/master/vignettes/ligand_target_signaling_path.md

Two important notes: 1) the regulatory potential is a potential of regulation, and cannot indicate whether this regulation is really up- or downregulation. 2) every ligand-target combination will get some non-zero value of regulatory potential. How are the regulatory potential scores calculated? For this I refer you to the original NicheNet paper and github. This figure provide an overview of the procedure:

[zhenzhenyang-psu]

Thanks very much for your informative reply, it's very helpful!