Linking proteins to signaling pathways for experiment design and evaluation.

PloS One
Illés J FarkasTamás Korcsmáros

Abstract

Biomedical experimental work often focuses on altering the functions of selected proteins. These changes can hit signaling pathways, and can therefore unexpectedly and non-specifically affect cellular processes. We propose PathwayLinker, an online tool that can provide a first estimate of the possible signaling effects of such changes, e.g., drug or microRNA treatments. PathwayLinker minimizes the users' efforts by integrating protein-protein interaction and signaling pathway data from several sources with statistical significance tests and clear visualization. We demonstrate through three case studies that the developed tool can point out unexpected signaling bias in normal laboratory experiments and identify likely novel signaling proteins among the interactors of known drug targets. In our first case study we show that knockdown of the Caenorhabditis elegans gene cdc-25.1 (meant to avoid progeny) may globally affect the signaling system and unexpectedly bias experiments. In the second case study we evaluate the loss-of-function phenotypes of a less known C. elegans gene to predict its function. In the third case study we analyze GJA1, an anti-cancer drug target protein in human, and predict for this protein novel signaling p...Continue Reading

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Citations

Mar 18, 2016·Omics : a Journal of Integrative Biology·Sneha Rai, Sonika Bhatnagar
Jul 24, 2014·Journal of Receptor and Signal Transduction Research·Akanksha GuptaSonika Bhatnagar
Oct 30, 2016·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Abdel Hady A Abdel WahabZakaria Y Abd Elmageed
Apr 20, 2017·Doklady. Biochemistry and Biophysics·E G RudimovL B Buravkova
Sep 7, 2017·Molecular Carcinogenesis·Deepshikha P KatareSwatantra K Jain
Jul 17, 2012·Trends in Cell Biology·Máté PálfyTamás Korcsmáros
Nov 27, 2021·Interdisciplinary Sciences, Computational Life Sciences·Xuting ZhangZunnan Huang

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Software Mentioned

QuickGO
UniProt
PathwayLinker
NeAT
Ensembl
HPRD
PharmGKB
MTOM
Cytoscape Web
Reactome

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