IID 2021: towards context-specific protein interaction analyses by increased coverage, enhanced annotation and enrichment analysis.

Improved bioassays have significantly increased the rate of identifying new protein-protein interactions (PPIs), and the number of detected human PPIs has greatly exceeded early estimates of human interactome size. These new PPIs provide a more complete view of disease mechanisms but precise understanding of how PPIs affect phenotype remains a challenge. It requires knowledge of PPI context (e.g. tissues, subcellular localizations), and functional roles, especially within pathways and protein complexes. The previous IID release focused on PPI context, providing networks with comprehensive tissue, disease, cellular localization, and druggability annotations. The current update adds developmental stages to the available contexts, and provides a way of assigning context to PPIs that could not be previously annotated due to insufficient data or incompatibility with available context categories (e.g. interactions between membrane and cytoplasmic proteins). This update also annotates PPIs with conservation across species, directionality in pathways, membership in large complexes, interaction stability (i.e. stable or transient), and mutation effects. Enrichment analysis is now available for all annotations, and includes multiple options; for example, context annotations can be analyzed with respect to PPIs or network proteins. In addition to tabular view or download, IID provides online network visualization. This update is available at http://ophid.utoronto.ca/iid.