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

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.