Abstract 2282: VIP: A system biology platform for cell line centric integrative analysis of molecular and functional genomics data

Abstract

Abstract Cancer is a heterogeneous disease that is classified by its tissue of origin or molecular characteristics such as genetic alterations that drive tumorigenesis. Large-scale efforts using loss-of-function genetic screens to systematically identify genes essential for the proliferation and survival of cancer cells provide a powerful approach for studying cancer biology and discovering drug targets. However, cancer cell lines from different lineages or molecular background vary in their dependencies on specific genes or pathways. Functional ablation of a gene may be only lethal in one segment of cancer cell lines harboring certain molecular deficiencies or activation of a specific oncogenic signaling pathway, a phenomenon called synthetic lethality. A key challenge here would be to identify the true synthetic lethal interactions from a combinatorially large number of possible interactions between molecular aberrations and gene-level sensitivity to functional perturbation. With recent advances in large-scale studies such as CCLE and Achilles, genome-wide functional genomics screens using CRISPR-Cas9 or shRNA technologies as well as comprehensive molecular profiles have become available for a large number of cancer cell lines. Here we present the Variant Interpretation Portal (VIP), a system biology tool designed to enable integrative analysis of molecular and functional genomics data in cell lines for identifying synthetic lethal interactions. VIP consists of a command-line pipeline and a web-based user interface. The VIP pipeline rigorously filters out germline events and classifies genomic variants into multiple functional tiers. The VIP web portal provides users with a graphic interface to perform exploratory visual analyses of associations between two variables or multiple variables, where a variable could be a genetic alteration or a gene-level sensitivity profile. VIP also enables systematic search for significant association between one variable, such as the sensitivity profile, vs. a database of variables such as histology or molecular attributes. VIP is optimized to perform real-time analytics and enables the incorporation and analysis of user-provided data. The code can be accessed from https://github.com/juferban/vip. Citation Format: Julio Fernandez, Ying Ding, Zhengyan Kan. VIP: A system biology platform for cell line centric integrative analysis of molecular and functional genomics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2282.