title: Identification of HPV integration and gene mutation in HeLa cell line by integrated analysis of RNA-Seq and MS/MS data.
abstract: HeLa cell line, which was derived from cervical carcinoma, provides an idea platform to study both the integration of human papillomavirus and the massive mutations occurring on the cancer cell genome. Proteogenomics is a field with the intersection of proteomics and genomics to perform gene annotation and identify gene mutation. In this work, we first identified the SNV/INDEL, structural variation (SV), and virus infection/integration events from RNA-Seq data of HeLa cell line; then, by applying proteogenomics strategy, we were able to detect some of the genomic events with the tandem mass spectrometry (MS/MS) data from the same sample. Furthermore, some of the mutated peptides were experimentally validated using multiple reaction monitoring technology. The integrated analysis of the RNA-Seq and MS/MS data not only renders the discovery of HeLa cell genome variations more credible but also illustrates a practical workflow for protein-coding mutation discovery in cancer-related studies.
authors.affiliation: †Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 1278 Ke Yuan Road, Shanghai 201203, China.|‡Key Laboratory of Systems Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Han
authors.initials: H
authors.lastname: Sun
authors.affiliation: §Department of Chemistry, Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200433, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: †Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 1278 Ke Yuan Road, Shanghai 201203, China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Lian
authors.affiliation: †Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 1278 Ke Yuan Road, Shanghai 201203, China.
authors.forename: Menghuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: ∥Department of Biomedical Informatics, Vanderbilt University School of Medicine, 2525 West End Avenue, Nashville, Tennessee 37232, United States.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: ∥Department of Biomedical Informatics, Vanderbilt University School of Medicine, 2525 West End Avenue, Nashville, Tennessee 37232, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: †Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 1278 Ke Yuan Road, Shanghai 201203, China.|‡Key Laboratory of Systems Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.affiliation: §Department of Chemistry, Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200433, China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
authors.affiliation: †Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 1278 Ke Yuan Road, Shanghai 201203, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xie
mesh_terms: D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D058977:Molecular Sequence Annotation; D009154:Mutation / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics* / Q000502:physiology*; D040901:Proteomics / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D016662:Virus Integration / Q000502:physiology*
keywords: HPV; HeLa; MRM; MS/MS; RNA-Seq; proteogenomics