Identification of HPV Integration and Gene Mutation in HeLa Cell Line by Integrated Analysis of RNA-Seq and MS/MS Data

J Proteome Res. 2015 Apr 3;14(4):1678-86. doi: 10.1021/pr500944c. Epub 2015 Mar 10.

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.

Keywords: HPV; HeLa; MRM; MS/MS; RNA-Seq; proteogenomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Variation*
  • HeLa Cells
  • Humans
  • Molecular Sequence Annotation
  • Mutation / genetics
  • Papillomaviridae / genetics*
  • Papillomaviridae / physiology*
  • Proteomics / methods*
  • Sequence Analysis, RNA / methods
  • Tandem Mass Spectrometry / methods
  • Virus Integration / physiology*