Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes.
Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes.
复制标题
DOI：
10.15252/msb.20167490
复制
发表时间：
2017-06-08
影响因子：
9.9
通讯作者：
Marcotte EM
中科院分区：
文献类型：
--
作者：
Drew K;Lee C;Huizar RL;Tu F;Borgeson B;McWhite CD;Ma Y;Wallingford JB;Marcotte EM
大分子蛋白质复合物执行细胞的许多基本功能，并且许多遗传疾病是由于破坏这些复合物的功能而引起的。目前，人们对定义完整的人类蛋白质复合物非常感兴趣，但最近发表的图谱缺乏全面的覆盖面。在这里，通过综合9,000多个已发表的质谱实验，我们提出了hu.MAP，迄今为止最全面和准确的人类蛋白质复合物图谱，包含> 4,600个总复合物，> 7,700个蛋白质和> 56,000个独特的相互作用，包括原始出版物未确定的数千个可信的蛋白质相互作用。MAP准确地概括了从学习过程中保留的已知复合物，该学习过程在用于比较集合的集合的新的定量度量（k-团）的帮助下进行了优化。我们地图中的绝大多数复合物都显著丰富了文献注释，并且地图总体上显示了许多疾病相关蛋白的覆盖率提高，正如我们详细描述的纤毛病。使用hu.MAP，我们预测和实验验证候选纤毛病疾病基因在体内的模型脊椎动物，发现CCDC 138，WDR 90，和KIAA 1328是新的纤毛基体/中心粒卫星蛋白，并确定ANKRD 55作为一个新的成员鞭毛内运输机械。通过提供对人蛋白质复合物的准确性和覆盖率的显著改进，hu.MAP（http：proteincomplexes.org）充当用于更好地理解人蛋白质的核心细胞功能和帮助确定人类疾病的机制基础的有价值的资源。
Macromolecular protein complexes carry out many of the essential functions of cells, and many genetic diseases arise from disrupting the functions of such complexes. Currently, there is great interest in defining the complete set of human protein complexes, but recent published maps lack comprehensive coverage. Here, through the synthesis of over 9,000 published mass spectrometry experiments, we present hu.MAP, the most comprehensive and accurate human protein complex map to date, containing > 4,600 total complexes, > 7,700 proteins, and > 56,000 unique interactions, including thousands of confident protein interactions not identified by the original publications. hu.MAP accurately recapitulates known complexes withheld from the learning procedure, which was optimized with the aid of a new quantitative metric (k‐cliques) for comparing sets of sets. The vast majority of complexes in our map are significantly enriched with literature annotations, and the map overall shows improved coverage of many disease‐associated proteins, as we describe in detail for ciliopathies. Using hu.MAP, we predicted and experimentally validated candidate ciliopathy disease genes in vivo in a model vertebrate, discovering CCDC138, WDR90, and KIAA1328 to be new cilia basal body/centriolar satellite proteins, and identifying ANKRD55 as a novel member of the intraflagellar transport machinery. By offering significant improvements to the accuracy and coverage of human protein complexes, hu.MAP (http://proteincomplexes.org) serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease.