Abstract 6307: ELViS : An R package for estimating copy number levels of viral genomic segments at base-resolution

Abstract Tumor virus is one of the major causes of human cancers, accounting for about 10-20% of their global incidence. Viral oncogenes in the tumor viruses promote tumorigenesis by deregulating host cancer genes. For instance, E6 and E7 proteins of human papillomavirus 16 (HPV16) induce the degradation of the protein products of tumor suppressor genes (TSGs) including p53 and pRb, to promote head and neck squamous cell carcinoma (HNSCC). Therefore, it is imperative to understand how differences in the dosage of viral genes affect cancer biology. However, how the relative and absolute abundance of each viral gene affects tumorigenesis and tumor biology has remained elusive, due to the difficulties in the analysis. Unlike human genomes that exist in two copies per cell, viral genome copies can take dynamic ranges, making copy number analyses challenging. Thus, we developed an R package ELViS that analyzes viral copy number change events from targeted DNA sequencing of whole viral genomes. In the first step, it takes aligned reads in the BAM file to generate base-resolution read depth and finds baseline regions based on the shape of the data. Next, to overcome the uneven base-resolution depths of targeted sequencing data and find copy number events, our framework performs joint segmentation in two-dimensional data space using both normalized read depths and Z-scores. In the simulation dataset, ELViS could detect deletions as small as 50bp and duplications as small as 500bp with F1 score &gt 0.75 at 50X coverage depths. ELViS provides base-resolution copy number change calls, along with publication-ready read depth line plots and cohort-level heatmap visualization of multiple data tracks with integrative clustering results. Citation Format: Jin-Young Lee, Hyo Young Choi, Jeremiah R. Holt, Xiaobei Zhao, Katherine A. Hoadley, D. Neil Hayes. ELViS : An R package for estimating copy number levels of viral genomic segments at base-resolution [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 6307.