To investigate networks based on protein-protein interaction (PPI) among the 25 causal proteins from the meta-analysis of the depression PWAS, we used GeNets, a web platform for network-based genomic analyses24. GeNets used the PPI information from the InWeb database, a curated and computationally derived PPI network of 420,000 PPIs of high and lower probability interactions63. GeNets implements an algorithm originally presented in Clauset et al64 that identifies so-called communities in a set of genes. A community is a set of genes that are more connected to one another than they are to other groups of genes. Additionally, GeNets enables gene set enrichment analysis on genes within a PPI network using the canonical pathways from 2199 gene sets in the MSigDB25. GeNets applied a hypergeometric test to obtain p-value for the gene set enrichment and used Bonferroni correction to adjust for multiple hypothesis testing.
