Select CEGS Publications

Rozenblatt-Rosen O, Deo RC, Padi M, Adelmant G, Calderwood MA, Rolland T, Grace M, Dricot A, Askenazi M, Tavares M, Pevzner SJ, Abderazzaq F, Byrdsong D, Carvunis AR, Chen AA, Cheng J, Correll M, Duarte M, Fan C, Feltkamp MC, Ficaro SB, Franchi R, Garg BK, Gulbahce N, Hao T, Holthaus AM, James R, Korkhin A, Litovchick L, Mar JC, Pak TR, Rabello S, Rubio R, Shen Y, Singh S, Spangle JM, Taşan M, Wanamaker S, Webber JT, Roecklein-Canfield J, Johannsen E, Barabási AL, Beroukhim R, Kieff E, Cusick ME, Hill DE, Münger K, Marto JA, Quackenbush J, Roth FP, DeCaprio JA, Vidal M.
Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.
Nature 2012; 487:491–5.
Using a systematic integrated pipeline we investigated at genome-scale perturbations of host interactome and transcriptome networks induced by individual gene products encoded by members of four functionally related, yet biologically distinct, families of DNA tumor viruses: polyomaviruses particularly SV40, papillomaviruses, adenovirus, and Epstein-Barr virus. This systematic analysis of host targets of viral proteins identified somatically mutated cancer genes with a success rate that is on par with and complementary to their identification by large-scale genome-wide efforts. This work substantiates the central hypothesis of this CEGS, that viral pathogens and human genetic variations similarly perturb properties of networks to induce disease.
Research Highlight, Nat Methods
Research Watch, Cancer Discovery
Research Highlight, Nat Rev Cancer
Research Highlight, Nat Rev Clin Oncol
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, 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.
Viral perturbations of host networks reflect disease etiology.
PLoS Comput Biol 2012; 8:e1002531.
Many virally implicated human diseases are associated with genetic alterations in particular disease susceptibility genes. For two human DNA tumor viruses, Epstein-Barr virus and human papillomavirus 16, we established a network-based framework to model the phenotypic consequences of the viral-host interactions. This viral “diseaseome” framework inaugurated in this report uncovers a path to decipher the interplay between viruses and disease phenotypes, in line with the premise that phenotypic effects of functional sequence variants are mediated through dynamic intracellular networks.
Simonis N, Rual JF, Lemmens I, Boxus M, Hirozane-Kishikawa T, Gatot JS, Dricot A, Hao T, Vertommen D, Legros S, Daakour S, Klitgord N, Martin M, Willaert JF, Dequiedt F, Navratil V, Cusick ME, Burny A, Lint CV, Hill DE, Tavernier J, Kettmann R, Vidal M, Twizere JC.
Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses.
Retrovirology 2012; 9:26.
This report mapped binary interactions between human host proteins and proteins of two highly related retroviruses: human T-cell lymphotropic viruses HTLV-1 and HTLV-2. HTLV-1 infection is associated with malignant lymphoproliferative disease whereas HTLV-2 infection is benign. Though these retroviruses are distinct from the human DNA tumor viruses which are the centerpiece of this CEGS, still this report nicely illustrates how to successfully generate and analyze viral-host perturbation networks.

Shapira SD, Gat-Viks I, Shum BO, Dricot A, de Grace MM, Wu L, Gupta PB, Hao T, Silver SJ, Root DE, Hill DE, Regev A, Hacohen N.
A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection.
Cell 2009; 139:1255-67.
This report employed a systematic strategy to elucidate the dynamic interactions between H1N1 influenza and its human host, combining yeast two-hybrid analysis and genome-wide expression profiling to discover human factors mediating viral-host interactions. The integrated strategy used here for uncovering complex viral-host relationships resembles the integrated pipeline this CEGS uses for uncovering perturbations of host networks by DNA tumor viruses.

Chatr-aryamontri A, Ceol A, Peluso D, Nardozza A, Panni S, Sacco F, Tinti M, Smolyar A, Castagnoli L, Vidal M, Cusick ME, Cesareni G.
VirusMINT: a viral protein interaction database.
Nucleic Acids Res 2009; 37:D669-73.
Any analysis of the perturbations caused by virus proteins on the cellular protein interaction network, the focus of this CEGS, requires some standard of comparison to what may already be known about viral-host interactions. This report fulfilled that need by compiling, in an easy to access database format, protein interactions between viral and human proteins reported in small-scale investigations.

Founding Publication

Calderwood MA, Venkatesan K, Xing L, Chase MR, Vazquez A, Holthaus AM, Ewence AE, Li N, Hirozane-Kishikawa T, Hill DE, Vidal M, Kieff E, Johannsen E.
Epstein-Barr virus and virus human protein interaction maps.
Proc Natl Acad Sci USA 2007; 104:7606-11.
Published prior to being granted CEGS support, this paper demonstrated that the genome-wide approaches now folded into our integrated CEGS pipeline would be successful, establishing the feasibility of high-throughput yeast two-hybrid mapping of viral-host binary protein interactions.

All CEGS Supported Publications

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