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 Rubio; Jarrod 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

doi:10.1371/journal.pcbi.1002531

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 journal › Article › peer-review

90 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 language	English (US)
Article number	e1002531
Journal	PLoS computational biology
Volume	8
Issue number	6
DOIs	https://doi.org/10.1371/journal.pcbi.1002531
State	Published - Jun 2012
Externally published	Yes

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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10.1371/journal.pcbi.1002531

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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), Article e1002531. https://doi.org/10.1371/journal.pcbi.1002531

Gulbahce, N, Yan, H, Dricot, A, Padi, M, Byrdsong, D, Franchi, R, Lee, DS, Rozenblatt-Rosen, O, Mar, JC, Calderwood, MA, Baldwin, A, Zhao, B, Santhanam, B, Braun, P, Simonis, N, Huh, KW, Hellner, K, Grace, M, Chen, A, Rubio, R, Marto, JA, Christakis, NA, Kieff, E, Roth, FP, Roecklein-Canfield, J, DeCaprio, JA, Cusick, ME, Quackenbush, J, Hill, DE, Münger, K, Vidal, M & Barabási, AL 2012, 'Viral perturbations of host networks reflect disease etiology', PLoS computational biology, vol. 8, no. 6, e1002531. https://doi.org/10.1371/journal.pcbi.1002531

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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.",

author = "Natali Gulbahce and Han Yan and Am{\'e}lie Dricot and Megha Padi and Danielle Byrdsong and Rachel Franchi and Lee, {Deok Sun} and Orit Rozenblatt-Rosen and Mar, {Jessica C.} and Calderwood, {Michael A.} and Amy Baldwin and Bo Zhao and Balaji Santhanam and Pascal Braun and Nicolas Simonis and Huh, {Kyung Won} and Karin Hellner and Miranda Grace and Alyce Chen and Renee Rubio and Marto, {Jarrod A.} and Christakis, {Nicholas A.} and Elliott Kieff and Roth, {Frederick P.} and Jennifer Roecklein-Canfield and DeCaprio, {James A.} and Cusick, {Michael E.} and John Quackenbush and Hill, {David E.} and Karl M{\"u}nger and Marc Vidal and Barab{\'a}si, {Albert L{\'a}szl{\'o}}",

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AU - Gulbahce, Natali

AU - Yan, Han

AU - Dricot, Amélie

AU - Padi, Megha

AU - Byrdsong, Danielle

AU - Franchi, Rachel

AU - Lee, Deok Sun

AU - Rozenblatt-Rosen, Orit

AU - Mar, Jessica C.

AU - Calderwood, Michael A.

AU - Baldwin, Amy

AU - Zhao, Bo

AU - Santhanam, Balaji

AU - Braun, Pascal

AU - Simonis, Nicolas

AU - Huh, Kyung Won

AU - Hellner, Karin

AU - Grace, Miranda

AU - Chen, Alyce

AU - Rubio, Renee

AU - Marto, Jarrod A.

AU - Christakis, Nicholas A.

AU - Kieff, Elliott

AU - Roth, Frederick P.

AU - Roecklein-Canfield, Jennifer

AU - DeCaprio, James A.

AU - Cusick, Michael E.

AU - Quackenbush, John

AU - Hill, David E.

AU - Münger, Karl

AU - Vidal, Marc

AU - Barabási, Albert László

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AB - 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.

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Viral perturbations of host networks reflect disease etiology

Abstract

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