title: The BioPlex Network: A Systematic Exploration of the Human Interactome.
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.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Huttlin
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Ting
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Raphael J
authors.initials: RJ
authors.lastname: Bruckner
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Fana
authors.initials: F
authors.lastname: Gebreab
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Melanie P
authors.initials: MP
authors.lastname: Gygi
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: John
authors.initials: J
authors.lastname: Szpyt
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Tam
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Zarraga
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Colby
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Baltier
authors.affiliation: Department of Cell Biology and Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06519, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Guarani
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Laura Pontano
authors.initials: LP
authors.lastname: Vaites
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alban
authors.initials: A
authors.lastname: Ordureau
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ramin
authors.initials: R
authors.lastname: Rad
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Erickson
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Wühr
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Chick
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhai
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kolippakkam
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Mintseris
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Biogen, Cambridge, MA 02142, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Obar
authors.affiliation: Biogen, Cambridge, MA 02142, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Harris
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Biogen, Cambridge, MA 02142, USA.
authors.forename: Spyros
authors.initials: S
authors.lastname: Artavanis-Tsakonas
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mathew E
authors.initials: ME
authors.lastname: Sowa
authors.affiliation: Department of Cell Biology and Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06519, USA.
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joao A
authors.initials: JA
authors.lastname: Paulo
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: wade_harper@hms.harvard.edu.
authors.forename: J Wade
authors.initials: JW
authors.lastname: Harper
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: steven_gygi@hms.harvard.edu.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D006801:Humans; D013058:Mass Spectrometry; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
chemical_list: D011506:Proteins