Integrating Protein-protein Interaction Networks with Phenotypes Reveals Signs of Interactions

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2013 Nov 19

PMID 24240319

Citations 57

Authors

Arunachalam Vinayagam

Jonathan Zirin

Charles Roesel

Yanhui Hu

Bahar Yilmazel

Anastasia A Samsonova

Ralph A Neumuller

Stephanie E Mohr

Norbert Perrimon

Affiliations

Soon will be listed here.

Abstract

A major objective of systems biology is to organize molecular interactions as networks and to characterize information flow within networks. We describe a computational framework to integrate protein-protein interaction (PPI) networks and genetic screens to predict the 'signs' of interactions (i.e., activation-inhibition relationships). We constructed a Drosophila melanogaster signed PPI network consisting of 6,125 signed PPIs connecting 3,352 proteins that can be used to identify positive and negative regulators of signaling pathways and protein complexes. We identified an unexpected role for the metabolic enzymes enolase and aldo-keto reductase as positive and negative regulators of proteolysis, respectively. Characterization of the activation-inhibition relationships between physically interacting proteins within signaling pathways will affect our understanding of many biological functions, including signal transduction and mechanisms of disease.

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