We constructed a protein-protein interaction (PPI) network using the GeNets42 to determine whether the Alzheimer’s disease TWAS genes significantly interact with each other and with known Alzheimer’s disease associated proteins. GeNets create networks of connected proteins using evidence of physical interaction from the InWeb database, which contains 420,000 high-confidence pair-wise interactions involving 12,793 proteins67. Community structures of the underlying genes are displayed in GeNets. These “communities” are also called modules or clusters. This feature highlights genes that are more connected to one another than they are to other genes in other modules. To assess the statistical significance of PPI networks, GeNets applies a within-degree node-label permutation strategy to build random networks that mimic the structure of the original network and evaluates network connectivity parameters on these random networks to generate empirical distributions for comparison to the original network. In addition to PPI network analysis, GeNets allows for gene set enrichment analysis on genes within the PPI network. We used Molecular Signatures Database (MSigDB) Curated Gene Sets (C2), curated from various sources such as online pathway databases, the biomedical literature, and
