A reference map of the human binary protein interactome
A reference map of the human binary protein interactome
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DOI：
10.1038/s41586-020-2188-x
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发表时间：
2020-04-16
期刊：
影响因子：
64.8
通讯作者：
Calderwood, Michael A.
中科院分区：
文献类型：
--
作者：
Luck, Katja;Kim, Dae-Kyum;Calderwood, Michael A.
全面了解细胞组织和基因组功能需要全面了解介导基因型-表型关系的相互作用组网络（1，2）。在这里，我们提出了一个人类二元蛋白质相互作用的人类“全部”参考相互作用组图谱，或“HuRI”。HuRI有大约53，000种蛋白质-蛋白质相互作用，这种相互作用大约是小规模研究中高质量策划的相互作用的四倍。HuRI与基因组（3）、转录组（4）和蛋白质组（5）数据的整合使得能够在大多数生理或病理细胞背景下研究细胞功能。我们证明了HuRI在识别蛋白质-蛋白质相互作用的特定亚细胞作用方面的实用性。推断的组织特异性网络揭示了细胞背景特异性功能形成的一般原则，并阐明了可能构成孟德尔疾病组织特异性表型的潜在分子机制。HuRI是一个系统性的蛋白质组参考，将基因组变异与表型结果联系起来。
Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships(1,2). Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome(3), transcriptome(4) and proteome(5) data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes.