Proteogenomic Analysis of Human Chromosome 9‑Encoded Genes from Human Samples and Lung Cancer Tissues

The Chromosome-centric Human Proteome
Project (C-HPP) was recently
initiated as an international collaborative effort. Our team adopted
chromosome 9 (Chr 9) and performed a bioinformatics and proteogenomic
analysis to catalog Chr 9-encoded proteins from normal tissues, lung
cancer cell lines, and lung cancer tissues. Approximately 74.7% of
the Chr 9 genes of the human genome were identified, which included
approximately 28% of missing proteins (46 of 162) on Chr 9 compared
with the list of missing proteins from the neXtProt Master Table (2013-09).
In addition, we performed a comparative proteomics analysis between
normal lung and lung cancer tissues. On the basis of the data analysis,
15 proteins from Chr 9 were detected only in lung cancer tissues.
Finally, we conducted a proteogenomic analysis to discover Chr 9-residing
single nucleotide polymorphisms (SNP) and mutations described in the
COSMIC cancer mutation database. We identified 21 SNPs and four mutations
containing peptides on Chr 9 from normal human cells/tissues and lung
cancer cell lines, respectively. In summary, this study provides valuable
information of the human proteome for the scientific community as
part of C-HPP. The mass spectrometry proteomics data have been deposited
to the ProteomeXchange Consortium with the data set identifier PXD000603.

以染色体为中心的人类蛋白质组计划（Chromosome-centric Human Proteome Project, C-HPP）作为一项国际协作研究项目于近期启动。本研究团队承接9号染色体（Chr 9）相关研究任务，通过生物信息学与蛋白质基因组学分析，对正常组织、肺癌细胞系及肺癌组织中由9号染色体编码的蛋白质进行系统性编目。本次研究共鉴定出人类基因组中约74.7%的9号染色体基因，相较于2013年9月发布的neXtProt主表缺失蛋白质列表，本研究涵盖了9号染色体上约28%的缺失蛋白质（共计162个中的46个）。此外，团队针对正常肺组织与肺癌组织开展了比较蛋白质组学分析，经数据分析发现，共有15种9号染色体编码的蛋白质仅在肺癌组织中被检测到。最后，本研究通过蛋白质基因组学分析，挖掘了COSMIC癌症突变数据库中记载的9号染色体单核苷酸多态性（Single Nucleotide Polymorphism, SNP）与突变信息，分别从正常人体细胞/组织及肺癌细胞系中鉴定出21个携带单核苷酸多态性的肽段与4个携带突变的肽段。综上，本研究作为C-HPP的组成部分，为全球科学界提供了极具价值的人类蛋白质组相关研究数据。本研究产生的质谱蛋白质组学数据已提交至蛋白质组交换联盟（ProteomeXchange Consortium），数据集标识符为PXD000603。