Dynamic Modularity in Protein Interaction Networks Predicts Breast Cancer Outcome

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2009 Feb 3

PMID 19182785

Citations 349

Authors

Ian W Taylor

Rune Linding

David Warde-Farley

Yongmei Liu

Catia Pesquita

Daniel Faria

Shelley Bull

Tony Pawson

Quaid Morris

Jeffrey L Wrana

Affiliations

Soon will be listed here.

Abstract

Changes in the biochemical wiring of oncogenic cells drives phenotypic transformations that directly affect disease outcome. Here we examine the dynamic structure of the human protein interaction network (interactome) to determine whether changes in the organization of the interactome can be used to predict patient outcome. An analysis of hub proteins identified intermodular hub proteins that are co-expressed with their interacting partners in a tissue-restricted manner and intramodular hub proteins that are co-expressed with their interacting partners in all or most tissues. Substantial differences in biochemical structure were observed between the two types of hubs. Signaling domains were found more often in intermodular hub proteins, which were also more frequently associated with oncogenesis. Analysis of two breast cancer patient cohorts revealed that altered modularity of the human interactome may be useful as an indicator of breast cancer prognosis.

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