Proteogenomics in the context of the Human Proteome Project (HPP)

<b>Introduction</b>: The technological and scientific progress performed in the Human Proteome Project (HPP) has provided to the scientific community a new set of experimental and bioinformatic methods in the challenging field of shotgun and SRM/MRM-based Proteomics. The requirements for a protein to be considered experimentally validated are now well-established, and the information about the human proteome is available in the neXtProt database, while targeted proteomic assays are stored in SRMAtlas. However, the study of the missing proteins continues being an outstanding issue. <b>Areas covered</b>: This review is focused on the implementation of proteogenomic methods designed to improve the detection and validation of the missing proteins. The evolution of the methodological strategies based on the combination of different omic technologies and the use of huge publicly available datasets is shown taking the Chromosome 16 Consortium as reference. <b>Expert commentary</b>: Proteogenomics and other strategies of data analysis implemented within the C-HPP initiative could be used as guidance to complete in a near future the catalog of the human proteins. Besides, in the next years, we will probably witness their use in the B/D-HPP initiative to go a step forward on the implications of the proteins in the human biology and disease.

<b>引言</b>：人类蛋白质组计划（Human Proteome Project, HPP）所取得的技术与科学进展，为全球科研学界在极具挑战的鸟枪法蛋白质组学及基于选择反应监测/多反应监测（SRM/MRM）的蛋白质组学领域提供了一套全新的实验与生物信息学研究方法。当前，蛋白质经实验验证的判定标准已明确确立，人类蛋白质组的相关信息可通过neXtProt数据库查询获取，而靶向蛋白质组学检测数据集则存储于SRMAtlas数据库中。不过，缺失蛋白质的相关研究仍是本领域亟待突破的突出课题。
<b>涵盖领域</b>：本综述聚焦于旨在提升缺失蛋白质检测与验证效能的蛋白质基因组学方法的落地应用，并以16号染色体联盟为典型参考案例，展示了融合多组学技术的方法策略迭代历程，以及海量公开数据集的应用路径。
<b>专家评述</b>：人类蛋白质组计划染色体组倡议（C-HPP）中所采用的蛋白质基因组学及其他数据分析策略，可作为未来完善人类蛋白质目录的重要参考指引。此外，未来数年内，这类方法有望在生物/疾病驱动的人类蛋白质组计划（B/D-HPP）中得到推广应用，以进一步深化对蛋白质在人类生物学与疾病发生发展中作用机制的研究。