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Cell. 2015 Jul 16;162(2):425-40. doi: 10.1016/j.cell.2015.06.043.

The BioPlex Network: A Systematic Exploration of the Human Interactome.

Author information

  • 1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • 2Department of Cell Biology and Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06519, USA.
  • 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Biogen, Cambridge, MA 02142, USA.
  • 4Biogen, Cambridge, MA 02142, USA.
  • 5Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: wade_harper@hms.harvard.edu.
  • 6Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: steven_gygi@hms.harvard.edu.

Abstract

Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors.

PMID:
26186194
PMCID:
PMC4617211
DOI:
10.1016/j.cell.2015.06.043
[PubMed - indexed for MEDLINE]
Free PMC Article
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