TCPGdb: A comprehensive T cell perturbation genomics database for identification of critical T cell regulators

Large parallel genetic screens have been used to identified targets and regulators that enhance T cell antitumor capability and persistence in tumor microenvironment. We hypothesized that by combining the pooled screen data from multiple independent genetic screens we could provide a systematic, comprehensive, and robust analysis of the effect of gene perturbation on T-cell based immunotherapies. After collecting data from previously published T cell screens, including CRISPR-based and ORF-based screens, through Gene Expression Omnibus (GEO), we reprocessed the gene hits summary and conducted a pathway enrichment analysis. A T cell screen perturbation score (TPS) metric was employed to quantify the impact of a gene perturbation on T cell function. Additionally, gene expression data (both bulk RNA level and single-cell RNA level) from autoimmune disease cohort and T cell-derived cancer patients were incorporated to gain further insight on gene perturbations that potentially augment T cell proliferation. We integrated all data and analysis on 35 T cells screens into our state-of-the-art T cell perturbation genomics database (TCPGdb), which is accessible through our webserver (http://tcpgdb.sidichenlab.org/) and allows users to interactively explore the impact of query genes on T cell function.