Dynamic modularity in protein interaction networks predicts breast cancer outcome

被引：533

作者：

Taylor, Ian W. ^{[1
,2
]}

Linding, Rune ^{[1
,3
]}

Warde-Farley, David ^{[4
,5
]}

Liu, Yongmei ^{[1
]}

Pesquita, Catia ^{[6
]}

Faria, Daniel ^{[6
]}

Bull, Shelley ^{[1
,7
]}

Pawson, Tony ^{[1
,2
]}

Morris, Quaid ^{[4
,5
]}

Wrana, Jeffrey L. ^{[1
,2
]}

机构：

[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[2] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[3] Inst Canc Res, Sect Cell, Mol & Syst Sect, Cellular & Mol Log Team, London SW3 6JB, England

[4] Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada

[5] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada

[6] Univ Lisbon, Fac Sci, P-1749016 Lisbon, Portugal

[7] Univ Toronto, Sch Publ Hlth, Toronto, ON M5T 3M7, Canada

来源：

NATURE BIOTECHNOLOGY | 2009年 / 27卷 / 02期

基金：

加拿大自然科学与工程研究理事会;

关键词：

INTERACTION DATABASE; DATA SETS; EXPRESSION; SIGNATURE; BIOLOGY; GENES; CELLS; TOOL;

D O I：

10.1038/nbt.1522

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：199 / 204

页数：6

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