DIGGER 2.0: digging into the functional impact of differential splicing on human and mouse disorders.

Changes in alternative splicing between groups or conditions contribute to protein-protein interaction rewiring, a consequence often neglected in data analysis. The web server and database DIGGER overcomes this limitation by augmenting a protein-protein interaction network with domain-domain interactions and splicing information. Here, we present DIGGER 2.0, which now features both experimental and newly added predicted domain-domain interactions. In addition to the human interactome, DIGGER 2.0 adds support for mouse as an important model organism. Additionally, we integrated the splicing analysis tool NEASE, which allows users to perform online splicing- and interactome-informed enrichment analysis on RNA-seq data. In two application cases (multiple sclerosis and mice models of cardiac diseases), we show the utility of DIGGER 2.0 for deeper exploration and functional interpretation of changes in alternative splicing in human and mouse disorders. DIGGER 2.0 is available at https://exbio.wzw.tum.de/digger/.