Abstract B022: TEDEdb: Transposable element differential expression database

Abstract Epigenetic therapies that induce global DNA hypomethylation activate transcriptionally repressed transposable elements (TEs). The activation of a class of TEs known as human endogenous retroviruses (HERVs) can trigger an innate antiviral response in cells called “viral mimicry”. Viral mimicry induced by aberrantly expressed HERVs stimulates interferon signaling genes resulting in an adaptive immune response that can ultimately lead to immunogenic cell death. This heightened immune activity can enhance the efficacy of immune checkpoint inhibitor therapies. Identifying cancers that are susceptible to a viral mimicry response or treatment regimens that induce aberrant transcription of TEs has not yet been fully explored. Recent computational tools enable the measurement of TE signal from short-read RNA-seq data and several large-scale reprocessing pipelines have uniformly processed RNA-seq data of cancer cell lines treated with epigenetic and cytotoxic drugs. However, these large-scale pipelines omit the quantification of TEs. To address this gap and fully utilize publicly available data, we have developed a computational pipeline and database of TE expression for more than 7,000 samples from 220 cancer cell lines treated with over 700 cytotoxic and epigenetic drugs, yielding over 2,100 differential expression experiments. To illustrate the usefulness of this database, we ranked drugs by %TE activation and found that the top three targets were DNMT (Decitabine), CDK9 (MC180295), and Topoisomerase II (Doxorubicin). We enable the exploration of this dataset by implementing several meta-analysis methods and visualizations made available as an interactive web application. This database and web application can serve as a valuable resource for the cancer and epigenetics community by enabling hypothesis generation and providing insights into how specific drugs may induce TE expression. Citation Format: Gennaro H Calendo, Morgan Chaunzwa, Iman Dehzangi, Jozef Madzo, Jean-Pierre Issa. TEDEdb: Transposable element differential expression database [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B022.