Comprehensive characterization of transposable element expression reveals regulatory circuitry and clinical implications in cancers

Abstract

Transposable elements (TEs) constitute nearly half of the human genome and have crucial roles in regulatory networks and clinical utility in cancers. However, the expression profiles at a single-element resolution remain unexplored. By integrating multiomics data from ∼10,000 samples and 1000 cancer cell lines, we established an expression atlas of 95,512 individual TEs across 980 subfamilies. Transcription factors and RNA binding proteins that are broadly associated with expressed TEs were involved in cancer-related signaling pathways (e.g., MYC activity). We identified 264,252 TEs as putative cis-regulatory elements associated with oncogenic pathways such as inflammatory response. We analyzed alterations in TE expression in tumors and their associations with clinical relevance and responses to more than 1000 anticancer drugs. Last, we developed the Atlas of Transposon Expression in Cancer (ATEC), a TE data portal enabling users to explore TE expression patterns, putative regulatory networks, and clinical significance. Overall, this study established a comprehensive resource for TEs across cancer types.