Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto M5T 3L9, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON M5S, Canada.
J Proteome Res. 2021 Jan 1;20(1):444-452. doi: 10.1021/acs.jproteome.0c00502. Epub 2020 Oct 27.
In-depth analysis of the human genome sequence has led to the annotation of approximately 20,000 human protein-coding genes. Although mass spectrometry (MS)-based workflows have made a great headway in achieving near genome-wide coverage, an equivalent complete map of the human proteome remains elusive. Delineating the spatial distribution of all human proteins at the organ, tissue, and cellular level can offer insight into health and disease and represents an excellent reference for the discovery of biomarkers and therapeutic targets. Here, we performed label-free liquid chromatography coupled to tandem MS (LC-MS/MS) to profile the normal human proteome. In total, we analyzed 117 samples from 46 normal tissues and organs at autopsy. Our high-resolution MS approach allowed for the quantification of 10,438 unique proteins. In order to expand our coverage of the human proteome, we combined our previously published biological fluid proteomic data from healthy individuals. We considered data from seven biological fluids, including urine, cerebrospinal fluid, synovial fluid, seminal plasma, sweat, cervical vaginal fluid, and nipple aspirate fluid. Overall, we generated tandem mass spectra corresponding to 13,028 unique human protein-coding genes. Although our analysis did not accomplish complete proteome coverage, it should be an important complementary resource for future biomarker discovery.
对人类基因组序列的深入分析导致了大约 20,000 个人类蛋白质编码基因的注释。尽管基于质谱(MS)的工作流程在实现近全基因组覆盖方面取得了重大进展,但人类蛋白质组的完整图谱仍然难以捉摸。描绘所有人类蛋白质在器官、组织和细胞水平的空间分布可以深入了解健康和疾病,并为发现生物标志物和治疗靶点提供极好的参考。在这里,我们进行了无标记的液相色谱-串联质谱(LC-MS/MS)分析,以描绘正常人类蛋白质组。总共,我们分析了来自 46 个正常组织和器官的 117 个尸检样本。我们的高分辨率 MS 方法允许定量 10,438 个独特的蛋白质。为了扩大我们对人类蛋白质组的覆盖范围,我们结合了我们之前从健康个体中发表的生物体液蛋白质组学数据。我们考虑了来自七种生物体液的数据,包括尿液、脑脊液、滑液、精液、汗液、宫颈阴道液和乳头吸出液。总体而言,我们生成了对应于 13,028 个人类蛋白质编码基因的串联质谱。虽然我们的分析没有完成完整的蛋白质组覆盖,但它应该是未来生物标志物发现的重要补充资源。