DIGGER: exploring the functional role of alternative splicing in protein interactions.

Markus List,Tim Kacprowski,Jan Baumbach,Olga Tsoy,Olga V Kalinina,Alexander Gress,Kevin Yuan,Zakaria Louadi

doi:10.1093/nar/gkaa768

Abstract

Alternative splicing plays a major role in regulating the functional repertoire of the proteome. However, isoform-specific effects to protein-protein interactions (PPIs) are usually overlooked, making it impossible to judge the functional role of individual exons on a systems biology level. We overcome this barrier by integrating protein-protein interactions, domain-domain interactions and residue-level interactions information to lift exon expression analysis to a network level. Our user-friendly database DIGGER is available at https://exbio.wzw.tum.de/digger and allows users to seamlessly switch between isoform and exon-centric views of the interactome and to extract sub-networks of relevant isoforms, making it an essential resource for studying mechanistic consequences of alternative splicing.

Highlights

Alternative splicing (AS) refers to differences in the processing of transcripts allowing to synthesize different protein variants from the same gene
Recent studies emphasize the considerable influence of AS on human protein-protein interactions (PPIs)
DIGGER closes this gap in order to help biomedical researchers to address the complexity in visualizing and analyzing the functional impacts of AS in a user-friendly fashion and on multiple levels, ranging from protein isoforms, via domains, down to exons

Summary

Introduction

Alternative splicing (AS) refers to differences in the processing of transcripts (e.g. exon skipping, intron retention etc.) allowing to synthesize different protein variants from the same gene. These protein variants, called isoforms, can vary in their functionality or even have opposite roles [1]. Climente-Gonzalez et al showed that around 30% of all isoform switches in tumor cells affect domains that mediate protein interaction [12]. This suggests a widespread impact of AS in the human interactome that is currently neglected [13]

Methods

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Discussion

Conclusion