Abstract 2391: Comprehensive quantification and annotation of viral gene integration and expression across thousands of human cancer models

Viral infections have been demonstrated to influence host gene expression and drive tumorigenesis. This study aims to systematically annotate genome integration and expression of ∼3000 exogenous and human-endogenous viral species across all public DepMap cancer cell lines, representing a diverse set of cancer types and lineages. Our preliminary results from this analysis pipeline successfully recapitulated known Human Papillomavirus (HpV strains 16, 18, 30 and 53) signatures in 12 cervical, 2 head and neck, and 4 engineered prostate cancer cell lines, demonstrating sensitivity at both the strain and gene levels. Associating these with genome-wide CRISPR screening data, we identified dependencies that were more correlated with viral presence rather than their respective lineages. Additionally, we observed expression of Epstein-Barr Virus(EBV) in multiple cancer types, a majority of which were of lymphoid lineage. We also found expression of the env gene of Human Endogenous Retrovirus-K (HERV-K113) in multiple lineages, with the highest average expression in skin cancers. By analyzing whole-genome sequencing we seek to identify viral integration sites in the cell lines’ genomes, to complement viral gene expression. From this large-scale multimodal analysis of features derived from genomic and transcriptomic data combined with gene dependencies, we aim to uncover potential viral contributions to oncogenesis and biomarker or target discovery. This will provide a foundational resource for understanding the role of viruses in cancer, offering new insights into viral-driven mechanisms of disease. Citation Format: Sowmya Iyer, Moore van Tienen, Phillipp Trollman, Yao He, William R. Sellers, Catarina D. Campbell. Comprehensive quantification and annotation of viral gene integration and expression across thousands of human cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2391.