Discovery of protein interaction networks shared by diseases

Lee Sam, Yang Liu, Jianrong Li, Carol Friedman, Yves A. Lussier

Research output: Chapter in Book/Report/Conference proceedingConference contribution

32 Scopus citations

Abstract

The study of protein-protein interactions is essential to define the molecular networks that contribute to maintain homeostasis of an organism's body functions. Disruptions in protein interaction networks have been shown to result in diseases in both humans and animals. Monogenic diseases disrupting biochemical pathways such as hereditary coagulopathies (e.g. hemophilia), provided a deep insight in the biochemical pathways of acquired coagulopathies of complex diseases. Indeed, a variety of complex liver diseases can lead to decreased synthesis of the same set of coagulation factors as in hemophilia. Similarly, more complex diseases such as different cancers have been shown to result from malfunctions of common proteins pathways. In order to discover, in high throughput, the molecular underpinnings of poorly characterized diseases, we present a statistical method to identify shared protein interaction network(s) between diseases. Integrating (i) a protein interaction network with (ii) disease to protein relationships derived from mining Gene Ontology annotations and the biomedical literature with natural language understanding (PhenoGO), we identified protein-protein interactions that were associated with pairs of diseases and calculated the statistical significance of the occurrence of interactions in the protein interaction knowledgebase. Significant correlations between diseases and shared protein networks were identified and evaluated in this study, demonstrating the high precision of the approach and correct non-trivial predictions, signifying the potential for discovery. In conclusion, we demonstrate that the associations between diseases are directly correlated to their underlying protein-protein interaction networks, possibly providing insight into the underlying molecular mechanisms of phenotypes and biological processes disrupted in related diseases.

Original languageEnglish (US)
Title of host publicationPacific Symposium on Biocomputing 2007, PSB 2007
Pages76-87
Number of pages12
StatePublished - Dec 1 2007
Externally publishedYes
EventPacific Symposium on Biocomputing, PSB 2007 - Maui, HI, United States
Duration: Jan 3 2007Jan 7 2007

Publication series

NamePacific Symposium on Biocomputing 2007, PSB 2007

Other

OtherPacific Symposium on Biocomputing, PSB 2007
CountryUnited States
CityMaui, HI
Period1/3/071/7/07

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ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Biomedical Engineering
  • Medicine(all)

Cite this

Sam, L., Liu, Y., Li, J., Friedman, C., & Lussier, Y. A. (2007). Discovery of protein interaction networks shared by diseases. In Pacific Symposium on Biocomputing 2007, PSB 2007 (pp. 76-87). (Pacific Symposium on Biocomputing 2007, PSB 2007).