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）作为一项国际合作项目于近期启动。本研究团队选取9号染色体（Chr 9），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编目。
本研究共鉴定出人类基因组中约74.7%的9号染色体基因，与2013年9月版neXtProt主表（neXtProt Master Table）中的缺失蛋白质列表相比，其中涵盖约28%的9号染色体缺失蛋白质（162个中的46个）。
此外，本研究还开展了正常肺组织与肺癌组织的比较蛋白质组学分析。基于数据分析结果，共鉴定出15种仅在肺癌组织中检出的9号染色体编码蛋白质。
最后，本研究开展了蛋白质基因组学分析，以探寻9号染色体上的单核苷酸多态性（single nucleotide polymorphisms，SNP）及COSMIC癌症突变数据库（COSMIC cancer mutation database）中收录的突变。我们分别从正常人类细胞/组织与肺癌细胞系中，鉴定出21个携带肽段的9号染色体SNP，以及4个携带肽段的9号染色体突变。
综上，本研究作为C-HPP的组成部分，为科学界提供了极具价值的人类蛋白质组相关信息。本研究的质谱（mass spectrometry）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。