Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
Division of Bioanalytics, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
Nat Biotechnol. 2019 Nov;37(11):1361-1371. doi: 10.1038/s41587-019-0298-5. Epub 2019 Nov 4.
Assigning functions to the vast array of proteins present in eukaryotic cells remains challenging. To identify relationships between proteins, and thereby enable functional annotation of proteins, we determined changes in abundance of 10,323 human proteins in response to 294 biological perturbations using isotope-labeling mass spectrometry. We applied the machine learning algorithm treeClust to reveal functional associations between co-regulated human proteins from ProteomeHD, a compilation of our own data and datasets from the Proteomics Identifications database. This produced a co-regulation map of the human proteome. Co-regulation was able to capture relationships between proteins that do not physically interact or colocalize. For example, co-regulation of the peroxisomal membrane protein PEX11β with mitochondrial respiration factors led us to discover an organelle interface between peroxisomes and mitochondria in mammalian cells. We also predicted the functions of microproteins that are difficult to study with traditional methods. The co-regulation map can be explored at www.proteomeHD.net .
给真核细胞中存在的大量蛋白质分配功能仍然具有挑战性。为了识别蛋白质之间的关系，从而实现蛋白质的功能注释，我们使用同位素标记质谱法测定了 10323 个人类蛋白质对 294 种生物扰动的丰度变化。我们应用机器学习算法 treeClust 从 ProteomeHD 中发现受调控的人类蛋白质之间的功能关联，这是我们自己的数据和 Proteomics Identifications 数据库数据集的汇编。这产生了人类蛋白质组的共调控图谱。共调控能够捕捉到不物理相互作用或共定位的蛋白质之间的关系。例如，过氧化物酶体膜蛋白 PEX11β 与线粒体呼吸因子的共调控使我们发现了哺乳动物细胞中过氧化物酶体和线粒体之间的细胞器接口。我们还预测了用传统方法难以研究的微蛋白的功能。共调控图谱可以在 www.proteomeHD.net 上进行探索。
