A map of human protein interactions derived from co-expression of human mRNAs and their orthologs.
A map of human protein interactions derived from co-expression of human mRNAs and their orthologs.
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DOI：
10.1038/msb.2008.19
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发表时间：
2008
影响因子：
9.9
通讯作者：
Marcotte, Edward M.
中科院分区：
文献类型：
--
作者：
Ramani, Arun K.;Li, Zhihua;Hart, G. Traver;Carlson, Mark W.;Boutz, Daniel R.;Marcotte, Edward M.
人类蛋白质相互作用网络将提供对细胞分子组织的全局见解，并为人类疾病建模提供框架，但该网络的大规模需要新的方法。我们报告了从间接证据推断出的人类蛋白质之间的7000种物理关联：人类mRNA共表达模式与其他五种真核生物中同源基因的共表达模式的比较，我们证明了在相同的物理复合物中识别蛋白质。为了评估预测物理关联的准确性，我们应用定量质谱枪蛋白质组学来测量天然生化分离过程中3013种人类蛋白质的洗脱谱，系统地证明了假定的相互作用伙伴倾向于共同沉积。我们进一步验证了与Williams-Beuren综合征相关的核糖体生物发生相关的未表征蛋白，包括WBSCR20C。因此，该荟萃分析利用了非蛋白质数据，但成功地预测了关联，包括5589种新的人类物理蛋白质关联，测量精度为54±10%，与直接的大规模相互作用分析相当。新的关联的推导保守的体内现象有力地证明了它们的生物学相关性。
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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影响因子：
12.3
作者：
Hart GT;Ramani AK;Marcotte EM
通讯作者：
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