Viral perturbations of host networks reflect disease etiology

Natali Gulbahce, Han Yan, Amélie Dricot, Megha Padi, Danielle Byrdsong, Rachel Franchi, Deok Sun Lee, Orit Rozenblatt-Rosen, Jessica C. Mar, Michael A. Calderwood, Amy Baldwin, Bo Zhao, Balaji Santhanam, Pascal Braun, Nicolas Simonis, Kyung Won Huh, Karin Hellner, Miranda Grace, Alyce Chen, Renee RubioJarrod A. Marto, Nicholas A. Christakis, Elliott Kieff, Frederick P. Roth, Jennifer Roecklein-Canfield, James A. DeCaprio, Michael E. Cusick, John Quackenbush, David E. Hill, Karl Münger, Marc Vidal, Albert László Barabási

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia.

Original languageEnglish (US)
Article numbere1002531
JournalPLoS Computational Biology
Volume8
Issue number6
DOIs
StatePublished - Jun 2012

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

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  • Cite this

    Gulbahce, N., Yan, H., Dricot, A., Padi, M., Byrdsong, D., Franchi, R., Lee, D. S., Rozenblatt-Rosen, O., Mar, J. C., Calderwood, M. A., Baldwin, A., Zhao, B., Santhanam, B., Braun, P., Simonis, N., Huh, K. W., Hellner, K., Grace, M., Chen, A., ... Barabási, A. L. (2012). Viral perturbations of host networks reflect disease etiology. PLoS Computational Biology, 8(6), [e1002531]. https://doi.org/10.1371/journal.pcbi.1002531