Functional enrichment of alternative splicing events with NEASE reveals insights into tissue identity and diseases

Genome Biology

Markus List¹  Melissa Klug²  Chit Tong Lio³  Zakaria Louadi³  Amit Fenn³  Dario Bongiovanni⁴  Maria L. Elkjaer⁵  Zsolt Illes⁵  Tim Kacprowski⁶  Olga Tsoy⁷  Jan Baumbach⁸ 

[1] Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, 85354, Freising, Germany;Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, 85354, Freising, Germany;Department of Internal Medicine I, School of Medicine, University hospital rechts der Isar, Technical University of Munich, Munich, Germany;German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany;Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, 85354, Freising, Germany;Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607, Hamburg, Germany;Department of Internal Medicine I, School of Medicine, University hospital rechts der Isar, Technical University of Munich, Munich, Germany;German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany;Department of Cardiovascular Medicine, Humanitas Clinical and Research Center IRCCS and Humanitas University, Rozzano, Milan, Italy;Department of Neurology, Odense University Hospital, Odense, Denmark;Institute of Clinical Research, University of Southern Denmark, Odense, Denmark;Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;Division Data Science in Biomedicine, Peter L. Reichertz Institute for Medical Informatics of Technische Universität Braunschweig and Hannover Medical School, Braunschweig, Germany;Braunschweig Integrated Centre of Systems Biology (BRICS), TU Braunschweig, Braunschweig, Germany;Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607, Hamburg, Germany;Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607, Hamburg, Germany;Institute of Mathematics and Computer Science, University of Southern Denmark, Campusvej 55, 5000, Odense, Denmark;

关键词: Alternative splicing;    Differential splicing;    Functional enrichment;    Systems biology;    Protein-protein interactions;    Disease pathways;    Platelet activation;    Multiple sclerosis;    Dilated cardiomyopathy;   

DOI  :  10.1186/s13059-021-02538-1

来源: Springer

【 摘 要 】

Alternative splicing (AS) is an important aspect of gene regulation. Nevertheless, its role in molecular processes and pathobiology is far from understood. A roadblock is that tools for the functional analysis of AS-set events are lacking. To mitigate this, we developed NEASE, a tool integrating pathways with structural annotations of protein-protein interactions to functionally characterize AS events. We show in four application cases how NEASE can identify pathways contributing to tissue identity and cell type development, and how it highlights splicing-related biomarkers. With a unique view on AS, NEASE generates unique and meaningful biological insights complementary to classical pathways analysis.

【 授权许可】

CC BY