Prediction of interactions between HIV-1 and human proteins by information integration

Oznur Tastan, Yanjun Qi, Jaime G. Carbonell, Judith Klein-Seetharaman

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

110 Scopus citations

Abstract

Hwnan immunodeficiency virus-1 (HIV-1) in acquired immune deficiency syndrome (AIDS) relies on human host cell proteins in virtually every aspect of its life cycle. Knowledge of the set of interacting human and viral proteins would greatly contribute to our understanding of the mechanisms of infection and subsequently to the design of new therapeutic approaches. This work is the first attempt to predict the global set of interactions between HIV-1 and human host cellular proteins. We propose a supervised learning framework, where multiple information data sources are utilized, including cooccurrence of functional motifs and their interaction domains and protein classes, gene ontology annotations, posttranslational modifications, tissue distributions and gene expression profiles, topological properties of the human protein in the interaction network and the similarity of HIV-1 proteins to human proteins' known binding partners. We trained and tested a Random Forest (RF) classifier with this extensive feature set. The model's predictions achieved an average Mean Average Precision (MAP) score of 23%. Among the predicted interactions was for example the pair, HIV-1 protein tat and human vitamin D receptor. This interaction had recently been independently validated experimentally. The rank-ordered lists of predicted interacting pairs are a rich source for generating biological hypotheses. Amongst the novel predictions, transcription regulator activity. immune system process and macromolecular complex were the top most significant molecular function, process and cellular compartments, respectively.

Original languageEnglish (US)
Title of host publicationPacific Symposium on Biocomputing 2009, PSB 2009
Pages516-527
Number of pages12
StatePublished - 2009
Externally publishedYes
Event14th Pacific Symposium on Biocomputing, PSB 2009 - Kohala Coast, HI, United States
Duration: Jan 5 2009Jan 9 2009

Publication series

NamePacific Symposium on Biocomputing 2009, PSB 2009

Other

Other14th Pacific Symposium on Biocomputing, PSB 2009
Country/TerritoryUnited States
CityKohala Coast, HI
Period1/5/091/9/09

ASJC Scopus subject areas

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

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