PT  - JOURNAL ARTICLE
AU  - Adrian Bubie
AU  - Fabien Zoulim
AU  - Barbara Testoni
AU  - Brett Miles
AU  - Marshall Posner
AU  - Augusto Villanueva
AU  - Bojan Losic
TI  - Landscape of oncoviral genotype and co-infection via Human papilloma and Hepatitis B viral tumor in-situ profiling
AID  - 10.1101/2020.03.24.006130
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.24.006130
4099  - http://biorxiv.org/content/early/2020/03/25/2020.03.24.006130.short
4100  - http://biorxiv.org/content/early/2020/03/25/2020.03.24.006130.full
AB  - Hepatitis B virus (HBV) and human papillomavirus (HPV) infection are known risk factors for developing several cancers. However, the effect of viral genotype and co-infection in actually driving oncogenesis remains unclear. We have developed and deployed a new scalable, high throughput tool (ViralMine) for sensitive and precise oncoviral genotype deconvolution using tumor RNA sequencing data from 537 virally infected liver, cervical, and head and neck tumors. We provide the first comprehensive integrative landscape of tumor-viral gene expression, viral antigen immunogenicity, patient survival, and mutational profiling organized by tumor onco-viral genotype. We find that HBV and HPV genotype, and surprisingly high rates of multi-genotype co-infection, serve as significant predictors of patient survival, tumor immune responsiveness, and APOBEC activity modulation. Finally, we demonstrate that HPV genotype strongly associates with viral onco-gene expression over cancer type, implying expression may be similar across episomal and stochastic integration-based infections.Significance Statement We demonstrate that scalable, high-accuracy oncoviral genotyping, gene expression, and co-infection estimation is feasible from legacy tumor RNA-seq data. While HBV and HPV genotype are known risk factors for oncogenesis, viral genotype and co-infection are shown to strongly associate with disease progression, patient survival, mutational signatures, and putative tumor neoantigen immunogenicity, facilitating novel clinical associations with infections.