Functional topology in a network of protein interactions

N. Pržulj, Dennis A Wigle, I. Jurisica

Research output: Contribution to journalArticle

252 Citations (Scopus)

Abstract

Motivation: The building blocks of biological networks are individual protein-protein interactions (PPIs). The cumulative PPI data set in Saccharomyces cerevisiae now exceeds 78 000. Studying the network of these interactions will provide valuable insight into the inner workings of cells. Results: We performed a systematic graph theory-based analysis of this PPI network to construct computational models for describing and predicting the properties of lethal mutations and proteins participating in genetic interactions, functional groups, protein complexes and signaling pathways. Our analysis suggests that lethal mutations are not only highly connected within the network, but they also satisfy an additional property: their removal causes a disruption in network structure. We also provide evidence for the existence of alternate paths that bypass viable proteins in PPI networks, while such paths do not exist for lethal mutations. In addition, we show that distinct functional classes of proteins have differing network properties. We also demonstrate a way to extract and iteratively predict protein complexes and signaling pathways. We evaluate the power of predictions by comparing them with a random model, and assess accuracy of predictions by analyzing their overlap with MIPS database. Conclusions: Our models provide a means for understanding the complex wiring underlying cellular function, and enable us to predict essentiality, genetic interaction, function, protein complexes and cellular pathways. This analysis uncovers structure-function relationships observable in a large PPI network.

Original languageEnglish (US)
Pages (from-to)340-348
Number of pages9
JournalBioinformatics
Volume20
Issue number3
DOIs
StatePublished - Feb 12 2004
Externally publishedYes

Fingerprint

Protein Interaction Maps
Protein-protein Interaction
Topology
Proteins
Protein
Protein Interaction Networks
Interaction
Mutation
Signaling Pathways
Predict
Path
Prediction
Biological Networks
Saccharomyces Cerevisiae
Structure-function
Graph theory
Network Structure
Alternate
Computational Model
Building Blocks

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Computational Theory and Mathematics
  • Computer Science Applications

Cite this

Functional topology in a network of protein interactions. / Pržulj, N.; Wigle, Dennis A; Jurisica, I.

In: Bioinformatics, Vol. 20, No. 3, 12.02.2004, p. 340-348.

Research output: Contribution to journalArticle

Pržulj, N. ; Wigle, Dennis A ; Jurisica, I. / Functional topology in a network of protein interactions. In: Bioinformatics. 2004 ; Vol. 20, No. 3. pp. 340-348.
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