A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs

Abstract The human protein interaction network will offer global insights into the molecular organization of cells and provide a framework for modeling human disease, but the network's large scale demands new approaches. We report a set of 7000 physical associations among human proteins inferre...

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Main Authors: Arun K Ramani, Zhihua Li, G Traver Hart, Mark W Carlson, Daniel R Boutz, Edward M Marcotte
Format: Article
Language:English
Published: Springer Nature 2008-04-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb.2008.19
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author Arun K Ramani
Zhihua Li
G Traver Hart
Mark W Carlson
Daniel R Boutz
Edward M Marcotte
author_facet Arun K Ramani
Zhihua Li
G Traver Hart
Mark W Carlson
Daniel R Boutz
Edward M Marcotte
author_sort Arun K Ramani
collection DOAJ
description Abstract The human protein interaction network will offer global insights into the molecular organization of cells and provide a framework for modeling human disease, but the network's large scale demands new approaches. We report a set of 7000 physical associations among human proteins inferred from indirect evidence: the comparison of human mRNA co‐expression patterns with those of orthologous genes in five other eukaryotes, which we demonstrate identifies proteins in the same physical complexes. To evaluate the accuracy of the predicted physical associations, we apply quantitative mass spectrometry shotgun proteomics to measure elution profiles of 3013 human proteins during native biochemical fractionation, demonstrating systematically that putative interaction partners tend to co‐sediment. We further validate uncharacterized proteins implicated by the associations in ribosome biogenesis, including WBSCR20C, associated with Williams–Beuren syndrome. This meta‐analysis therefore exploits non‐protein‐based data, but successfully predicts associations, including 5589 novel human physical protein associations, with measured accuracies of 54±10%, comparable to direct large‐scale interaction assays. The new associations’ derivation from conserved in vivo phenomena argues strongly for their biological relevance.
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spelling doaj-art-c5d7a5ade6ef446ea70129876b144de12025-08-24T12:01:29ZengSpringer NatureMolecular Systems Biology1744-42922008-04-014111610.1038/msb.2008.19A map of human protein interactions derived from co‐expression of human mRNAs and their orthologsArun K Ramani0Zhihua Li1G Traver Hart2Mark W Carlson3Daniel R Boutz4Edward M Marcotte5Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of TexasCenter for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of TexasCenter for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of TexasDepartment of Biomedical Engineering, University of TexasCenter for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of TexasCenter for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of TexasAbstract The human protein interaction network will offer global insights into the molecular organization of cells and provide a framework for modeling human disease, but the network's large scale demands new approaches. We report a set of 7000 physical associations among human proteins inferred from indirect evidence: the comparison of human mRNA co‐expression patterns with those of orthologous genes in five other eukaryotes, which we demonstrate identifies proteins in the same physical complexes. To evaluate the accuracy of the predicted physical associations, we apply quantitative mass spectrometry shotgun proteomics to measure elution profiles of 3013 human proteins during native biochemical fractionation, demonstrating systematically that putative interaction partners tend to co‐sediment. We further validate uncharacterized proteins implicated by the associations in ribosome biogenesis, including WBSCR20C, associated with Williams–Beuren syndrome. This meta‐analysis therefore exploits non‐protein‐based data, but successfully predicts associations, including 5589 novel human physical protein associations, with measured accuracies of 54±10%, comparable to direct large‐scale interaction assays. The new associations’ derivation from conserved in vivo phenomena argues strongly for their biological relevance.https://doi.org/10.1038/msb.2008.19interactionsmass spectrometrynetworksproteomicssystems biology
spellingShingle Arun K Ramani
Zhihua Li
G Traver Hart
Mark W Carlson
Daniel R Boutz
Edward M Marcotte
A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs
Molecular Systems Biology
interactions
mass spectrometry
networks
proteomics
systems biology
title A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs
title_full A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs
title_fullStr A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs
title_full_unstemmed A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs
title_short A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs
title_sort map of human protein interactions derived from co expression of human mrnas and their orthologs
topic interactions
mass spectrometry
networks
proteomics
systems biology
url https://doi.org/10.1038/msb.2008.19
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