A proteome-scale map of the human interactome network

PMCID: PMC4266588.-- et al.Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ∼14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ∼30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a >broader> human interactome network than currently appreciated. The map also uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help >connect the dots> of the genomic revolution.This work was supported primarily by NHGRI grant R01/U01HG001715 awarded to M.V., D.E.H., F.P.R., and J.T. and in part by the following grants and agencies: NHGRI P50HG004233 to M.V., F.P.R., and A.-L.B.; NHLBI U01HL098166 subaward to M.V.; NHLBI U01HL108630 subaward to A.-L.B.; NCI U54CA112962 subaward to M.V.; NCI R33CA132073 to M.V.; NIH RC4HG006066 to M.V., D.E.H., and T.H.; NICHD ARRA R01HD065288, R21MH104766, and R01MH105524 to L.M.I.; NIMH R01MH091350 to L.M.I. and T.H.; NSF CCF-1219007 and NSERC RGPIN-2014-03892 to Y.X.; Canada Excellence Research Chair, Krembil Foundation, Ontario Research Fund–Research Excellence Award, Avon Foundation, grant CSI07A09 from Junta de Castilla y Leon (Valladolid, Spain), grant PI12/00624 from Ministerio de Economia y Competitividad (AES 2012, ISCiii, Madrid, Spain), and grant i-Link0398 from Consejo Superior de Investigaciones Científicas (CSIC, Madrid, Spain) to J.D.L.R.; Spanish Ministerio de Ciencia e Innovación (BIO2010-22073) and the European Commission through the FP7 project SyStemAge grant agreement n: 306240 to P.A.; Group-ID Multidisciplinary Research Partnerships of Ghent University, grant FWO-V G.0864.10 from the Fund for Scientific Research-Flanders and ERC Advanced Grant N° 340941 to J.T.; EMBO long-term fellowship to A.K.; Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative to M.V. I.L. is a postdoctoral fellow with the FWO-V. M.V. is a “Chercheur Qualifié Honoraire” from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium). Since performing the work described, C. Fontanillo has become an employee of Celgene Research SL, part of the Celgene Corporation.Peer Reviewe

A proteome-scale map of the human interactome network

Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand geno-type- phenotype relationships. Here, we describe a systematic map of similar to 14,000 high-quality human binary protein-protein interactions. At equal quality, this map is similar to 30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a "broader'' human interactome network than currently appreciated. The map also uncovers significant inter-connectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help "connect the dots'' of the genomic revolution