Advances and Utility of the Human Plasma Proteome

The study of proteins circulating in blood offers tremendous opportunities to diagnose, stratify, or possibly prevent diseases. With recent technological advances and the urgent need to understand the effects of COVID-19, the proteomic analysis of blood-derived serum and plasma has become even more important for studying human biology and pathophysiology. Here we provide views and perspectives about technological developments and possible clinical applications that use mass-spectrometry­(MS)- or affinity-based methods. We discuss examples where plasma proteomics contributed valuable insights into SARS-CoV-2 infections, aging, and hemostasis and the opportunities offered by combining proteomics with genetic data. As a contribution to the Human Proteome Organization (HUPO) Human Plasma Proteome Project (HPPP), we present the Human Plasma PeptideAtlas build 2021-07 that comprises 4395 canonical and 1482 additional nonredundant human proteins detected in 240 MS-based experiments. In addition, we report the new Human Extracellular Vesicle PeptideAtlas 2021-06, which comprises five studies and 2757 canonical proteins detected in extracellular vesicles circulating in blood, of which 74% (2047) are in common with the plasma PeptideAtlas. Our overview summarizes the recent advances, impactful applications, and ongoing challenges for translating plasma proteomics into utility for precision medicine.血液中循环蛋白质的研究，为疾病的诊断、病情分层乃至潜在预防提供了巨大机遇。随着近年技术进步与深入理解新型冠状病毒病（COVID-19）影响的迫切需求，基于血液来源血清与血浆的蛋白质组学分析，在人类生物学与病理生理学研究中的重要性进一步凸显。本文阐述了基于质谱（mass-spectrometry, MS）或亲和富集技术的蛋白质组学技术发展方向与潜在临床应用前景，并讨论了血浆蛋白质组学为SARS-CoV-2感染、衰老与止血过程提供重要研究见解的相关案例，以及蛋白质组学与遗传学数据结合所带来的研究机遇。作为对人类蛋白质组组织（Human Proteome Organization, HUPO）人类血浆蛋白质组计划（Human Plasma Proteome Project, HPPP）的贡献，本文推出了2021-07版人类血浆肽图谱（Human Plasma PeptideAtlas），该数据集涵盖了通过240项基于质谱的实验所检测到的4395种标准人类蛋白质与1482种额外的非冗余人类蛋白质。此外，本文还发布了全新的2021-06版人类细胞外囊泡肽图谱（Human Extracellular Vesicle PeptideAtlas），该数据集包含五项研究中于血液循环细胞外囊泡内检测到的2757种标准蛋白质，其中74%（2047种）与血浆肽图谱存在重叠。本综述总结了将血浆蛋白质组学转化应用于精准医学领域的最新进展、极具影响力的应用场景以及当前仍面临的各类挑战。