PT - JOURNAL ARTICLE AU - Edward L. Huttlin AU - Raphael J. Bruckner AU - Jose Navarrete-Perea AU - Joe R. Cannon AU - Kurt Baltier AU - Fana Gebreab AU - Melanie P. Gygi AU - Alexandra Thornock AU - Gabriela Zarraga AU - Stanley Tam AU - John Szpyt AU - Alexandra Panov AU - Hannah Parzen AU - Sipei Fu AU - Arvene Golbazi AU - Eila Maenpaa AU - Keegan Stricker AU - Sanjukta Guha Thakurta AU - Ramin Rad AU - Joshua Pan AU - David P. Nusinow AU - Joao A. Paulo AU - Devin K. Schweppe AU - Laura Pontano Vaites AU - J. Wade Harper AU - Steven P. Gygi TI - Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome AID - 10.1101/2020.01.19.905109 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.01.19.905109 4099 - http://biorxiv.org/content/early/2020/01/19/2020.01.19.905109.short 4100 - http://biorxiv.org/content/early/2020/01/19/2020.01.19.905109.full AB - Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins – half the proteome – in 293T cells and includes 118,162 interactions among 14,586 proteins; the second results from 5,522 immunoprecipitations in HCT116 cells. These networks model the interactome at unprecedented scale, encoding protein function, localization, and complex membership. Their comparison validates thousands of interactions and reveals extensive customization of each network. While shared interactions reside in core complexes and involve essential proteins, cell-specific interactions bridge conserved complexes, likely ‘rewiring’ each cell’s interactome. Interactions are gained and lost in tandem among proteins of shared function as the proteome remodels to produce each cell’s phenotype. Viewable interactively online through BioPlexExplorer, these networks define principles of proteome organization and enable unknown protein characterization.