Title: Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes - Molecular Systems Biology (2017)

Authors: Kevin Drew, Chanjae Lee, Ryan Huizar, Fan Tu, Blake Borgeson, Claire McWhite, Yun Ma, John Wallingford, Edward Marcotte

Abstract: Macromolecular protein complexes carry out many of the essential functions of cells, and many genetic diseases arise from disrupting the functions of such complexes. Currently there is great interest in defining the complete set of human protein complexes, but recent published maps lack comprehensive coverage. Here, through the synthesis of over 9,000 published mass spectrometry experiments, we present hu.MAP, the most comprehensive and accurate human protein complex map to date, containing >4,600 total complexes, >7,700 proteins and >56,000 unique interactions, including thousands of confident protein interactions not identified by the original publications. hu.MAP accurately recapitulates known complexes withheld from the learning procedure, which was optimized with the aid of a new quantitative metric (k-cliques) for comparing sets of sets. The vast majority of complexes in our map are significantly enriched with literature annotations and the map overall shows improved coverage of many disease-associated proteins, as we describe in detail for ciliopathies. Using hu.MAP, we predicted and experimentally validated candidate ciliopathy disease genes in vivo in a model vertebrate, discovering CCDC138, WDR90, and KIAA1328 to be new cilia basal body/centriolar satellite proteins, and identifying ANKRD55 as a novel member of the intraflagellar transport machinery. By offering significant improvements to the accuracy and coverage of human protein complexes, hu.MAP (http://proteincomplexes.org) serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease.

Downloads (56,716 Interactions were derived from a synthesis of three high-throughput proteomics datasets (1 Co-fractionation and 2 Affinity Capture-MS): Wan et al. (2015 PMID:26344197), Hein et al. (2015 PMID:26496610) and Huttlin et al. (2015 PMID:26186194) (Bioplex). Interactions with BioPlex or Hein et al. annotations involve at least one bait in the original AP-MS experiments. Matrix_Model annotations were ranked prey-prey relationships from AP-MS experiments. Wan et al. annotations were derived from co-fractionation experiments. Multiple_Evidences interactions were derived from a combination of the above experiments.): Microsoft Excel Format (XLS)