A complex-based reconstruction of the Saccharomyces cerevisiae interactome

Haidong Wang, Boyko Kakaradov, Sean R. Collins, Lena Karotki, Dorothea Fiedler, Michael Shales, Kevan M. Shokat, Tobias C. Walther, Nevan J. Krogan, Daphne Kollen

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Most cellular processes are performed by proteomic units that interact with each other. These units are often stoichiometrically stable complexes comprised of several proteins. To obtain a faithful view of the protein interactome we must view it in terms of these basic units (complexes and proteins) and the interactions between them. This study makes two contributions toward this goal. First, it provides a new algorithm for reconstruction of stable complexes from a variety of heterogeneous biological assays; our approach combines state-of-the-art machine learning methods with a novel hierarchical clustering algorithm that allows clusters to overlap. We demonstrate that our approach constructs over 40% more known complexes than other recent methods and that the complexes it produces are more biologically coherent even compared with the reference set. We provide experimental support for some of our novel predictions, identifying both a new complex involved in nutrient starvation and a new component of the eisosome complex. Second, we provide a high accuracy algorithm for the novel problem of predicting transient interactions involving complexes. We show that our complex level network, which we call ComplexNet, provides novel insights regarding the protein-protein interaction network. In particular, we reinterpret the finding that "hubs" in the network are enriched for being essential, showing instead that essential proteins tend to be clustered together in essential complexes and that these essential complexes tend to be large.

Original languageEnglish (US)
Pages (from-to)1361-1381
Number of pages21
JournalMolecular and Cellular Proteomics
Volume8
Issue number6
DOIs
StatePublished - Jun 1 2009

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Yeast
Saccharomyces cerevisiae
Proteins
Protein Interaction Maps
Starvation
Biological Assay
Proteomics
Cluster Analysis
Clustering algorithms
Nutrients
Learning systems
Assays
Food

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Cite this

A complex-based reconstruction of the Saccharomyces cerevisiae interactome. / Wang, Haidong; Kakaradov, Boyko; Collins, Sean R.; Karotki, Lena; Fiedler, Dorothea; Shales, Michael; Shokat, Kevan M.; Walther, Tobias C.; Krogan, Nevan J.; Kollen, Daphne.

In: Molecular and Cellular Proteomics, Vol. 8, No. 6, 01.06.2009, p. 1361-1381.

Research output: Contribution to journalArticle

Wang, H, Kakaradov, B, Collins, SR, Karotki, L, Fiedler, D, Shales, M, Shokat, KM, Walther, TC, Krogan, NJ & Kollen, D 2009, 'A complex-based reconstruction of the Saccharomyces cerevisiae interactome', Molecular and Cellular Proteomics, vol. 8, no. 6, pp. 1361-1381. https://doi.org/10.1074/mcp.M800490-MCP200
Wang, Haidong ; Kakaradov, Boyko ; Collins, Sean R. ; Karotki, Lena ; Fiedler, Dorothea ; Shales, Michael ; Shokat, Kevan M. ; Walther, Tobias C. ; Krogan, Nevan J. ; Kollen, Daphne. / A complex-based reconstruction of the Saccharomyces cerevisiae interactome. In: Molecular and Cellular Proteomics. 2009 ; Vol. 8, No. 6. pp. 1361-1381.
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