Architecture of the human interactome defines protein communities and disease networks

Nature
Edward L HuttlinJ Wade Harper

Abstract

The physiology of a cell can be viewed as the product of thousands of proteins acting in concert to shape the cellular response. Coordination is achieved in part through networks of protein-protein interactions that assemble functionally related proteins into complexes, organelles, and signal transduction pathways. Understanding the architecture of the human proteome has the potential to inform cellular, structural, and evolutionary mechanisms and is critical to elucidating how genome variation contributes to disease. Here we present BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein-coding genes from the human genome, and constitutes, to our knowledge, the largest such network so far. With more than 56,000 candidate interactions, BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins while enhancing network-based analyses of domain associations, subcellular localization, and co-complex formation. Unsupervised Markov clustering of interacting protein...Continue Reading

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Citations

Sep 22, 2017·International Journal of Molecular Sciences·Zhihua Du, Vladimir N Uversky
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Methods Mentioned

BETA
affinity purification
affinity-purification
transfection
PCR
immunoprecipitation
interaction
pull-downs
confocal microscopy

Software Mentioned

R
NDEx
CompPASS
Sequest
DisGeNET
Plus
AP
SQLite
BioGrid
MetaMorph

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