The BioPlex Network: A Systematic Exploration of the Human Interactome

By Edward L. Huttlin, Lily Ting, Raphael J. Bruckner, Fana Gebreab, Melanie P. Gygi, John Szpyt, Stanley Tam, G. Zárraga, G. Colby, Kurt Baltier and 19 more. Cell, 2015

1,351 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Cognitive Neuroscience, Experimental and Cognitive Psychology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d1efb71517512fe46b85b90ba4c65db16142c81f

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In Cognitive Neuroscience

Kathleen M. Jagodnik

In Molecular Biology

Citations in the corpus

MSFragger: ultrafast and comprehensive peptide identification in shotgun proteomics (2017, methodology): “We also applied MSFragger to a large-scale protein-interaction study using an AP–MS experimental workflow that consisted of 2,594 baits analyzed in technical duplicates 41 .”
G3BP1 is a tunable switch that triggers phase separation to assemble stress granules (2020, positive): “A composite protein-protein interaction (PPI) network was built by combining STRING (v10) (Szklarczyk et al., 2015), BioPlex (Huttlin et al., 2015), and InWeb (Hopkins et al., 2017), as well as three unbiased SG interactomes (Jain et al., 2016; Markmiller et al., 2018; Youn et al., 2018).”
The BioGRID interaction database: 2017 update (2016, methodology): “Since the advent of high-throughput approaches to detect protein (1– 3) and genetic interactions (4), the depth of coverage and accuracy of biological interaction networks has continued to improve (5,6), with increased resolution at the level of protein isoforms (7) and metabolites (8,9).”
Massive mining of publicly available RNA-seq data from human and mouse (2017, methodology): “This is likely because a part of BioPLEX is contained within hu.”
P-Body Purification Reveals the Condensation of Repressed mRNA Regulons. (2017, methodology): “4 Molecular Cell 68, 1–14, October 5, 2017 right) (Hein et al., 2015; Huttlin et al., 2015).”
The CASTOR proteins are arginine sensors for the mTORC1 pathway (2016, positive): “To identify potential GATOR2binding partners, we interrogated BioPlex, a database of human protein-protein interactions generated from immunoprecipitation followed by mass spectrometry of 2,594 proteins stably expressed in HEK293T cells (Huttlin et al., 2015).”