Abstract 4921: A user-friendly R Shiny web app for predicting cancer genetic dependencies using deep learning

Abstract

Abstract Understanding the genetic vulnerabilities (i.e., genetic dependencies) of cancer cells is crucial for developing novel anti-cancer treatments. The Cancer Dependency Map (DepMap) projects, conducted by the Broad Institute and Wellcome Sanger Institute, have performed comprehensive genome-wide CRISPR-Cas9 knockout screens across diverse cancer cell lines. These data resources have enabled computational biologists to glean insights into cancer genetic dependencies using sophisticated computational models. As different genomic mechanisms govern tumorigenesis and genetic vulnerability, the relationship between cancer genomics and genetic dependencies is nonlinear, making the prediction of genetic dependencies challenging. Addressing this challenge, we previously developed a deep learning model, namely DeepDEP, to predict cancer genetic dependencies using multi-omic profiles (Chiu et al. DOI:10.1126/sciadv.abh1275). DeepDEP has a transfer learning scheme that integrates genomic representations captured from unlabeled tumor samples of the Cancer Genome Atlas (TCGA) and genomic features that are predictive of genetic dependencies in cell lines. Such a design enables the application of DeepDEP to both cell lines and tumors. The model demonstrated superior performance compared to various conventional machine learning methods. Prediction results were validated using independent cell-line datasets and patient clinical data. Here, we developed an intuitive web application for DeepDEP which allows users to easily utilize the model on their in-house data. Users can simply indicate whether the query sample is derived from a cancer cell line or a tumor, upload any combination of mutation, gene expression, DNA methylation, and copy number alteration datasets, and view the predicted dependencies of 1,298 cancer-relevant genes. Along with the genetic dependency predictions, users are provided with model performance metrics, detailed gene annotations, and links to useful resources such as Ensembl and COSMIC. Our web application features a variety of interactive visualizations to guide users to interpret the results at the levels of individual genes and pathways. The tool has two supplemental modules to enhance its functionality. One allows users to search for similar cell lines to the query sample within the DepMap project or for similar tumors within the TCGA project. The other supplemental module provides data exploration tools for pre-calculated predictions across all TCGA tumors. In summary, this user-friendly web application provides researchers with access to deep learning predictions of cancer genetic dependencies with various interactive visualization and analysis tools. It is anticipated that this application will facilitate the study of cancer genetic dependencies and enhance the efficiency of anti-cancer drug discovery. Citation Format: Michael J. Kasper, Li-Ju Wang, Michael Ning, Yufei Huang, Yu-Chiao Chiu. A user-friendly R Shiny web app for predicting cancer genetic dependencies using deep learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4921.