Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH Royal Institute of Technology , Tomtebodavägen 23, SE-171 65 Solna, Sweden.
Departments of Computational Medicine & Bioinformatics, Internal Medicine, and Human Genetics and School of Public Health, University of Michigan , Ann Arbor, Michigan 48109-2218, United States.
J Proteome Res. 2017 Dec 1;16(12):4299-4310. doi: 10.1021/acs.jproteome.7b00467. Epub 2017 Oct 10.
Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization's Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements. We then present the latest 2017-04 build of Human Plasma PeptideAtlas, which yields ∼43 million peptide-spectrum matches and 122,730 distinct peptide sequences from 178 individual experiments at a 1% protein-level FDR globally across all experiments. Applying the latest Human Proteome Project Data Interpretation Guidelines, we catalog 3509 proteins that have at least two non-nested uniquely mapping peptides of nine amino acids or more and >1300 additional proteins with ambiguous evidence. We apply the same two-peptide guideline to historical PeptideAtlas builds going back to 2006 and examine the progress made in the past ten years in plasma proteome coverage. We also compare the distribution of proteins in historical PeptideAtlas builds in various RNA abundance and cellular localization categories. We then discuss advances in plasma proteomics based on targeted mass spectrometry as well as affinity assays, which during early 2017 target ∼2000 proteins. Finally, we describe considerations about sample handling and study design, concluding with an outlook for future advances in deciphering the human plasma proteome.
人血浆提供了一个高度可及的窗口，可以了解健康和疾病个体的蛋白质组。自 2002 年成立以来，人类蛋白质组组织的人类血浆蛋白质组计划（HPPP）一直在推动人类血浆蛋白质组的研究和理解的进展，以及确定其成分的丰度和修饰。在 2017 年，我们回顾了 HPPP 的历史和人类血浆蛋白质组学的一般进展，包括最近的一些成就。然后，我们展示了最新的 2017-04 版人类血浆肽图谱，该图谱从全球所有实验中 178 个独立实验的 1%蛋白质水平 FDR 获得了约 4300 万肽谱匹配和 122730 个独特肽序列。应用最新的人类蛋白质组计划数据解释指南，我们将至少有两个非嵌套的、独特映射的 9 个氨基酸或更长和 >1300 个具有模糊证据的额外蛋白质的 3509 个蛋白质编入目录。我们将相同的双肽准则应用于回溯到 2006 年的历史肽图谱构建，并检查过去十年在血浆蛋白质组覆盖方面取得的进展。我们还比较了在不同 RNA 丰度和细胞定位类别中历史肽图谱构建中的蛋白质分布。然后，我们根据靶向质谱和亲和测定法讨论了血浆蛋白质组学的进展，这两种方法在 2017 年初靶向约 2000 个蛋白质。最后，我们描述了关于样本处理和研究设计的考虑因素，最后展望了未来在破译人类血浆蛋白质组方面的进展。
