G-quadruplexes (G4s) are non-canonical four-stranded structures and emerge as novel genetic regulatory elements. However, a comprehensive genomic annotation of endogenous G4s (eG4s) and systematic characterization of their regulatory network are still lacking, raising great challenges for eG4 research. Here, we present EndoQuad to address these pressing issues by integrating high-throughput experimental data. First, based on more than 1200 high-quality genome-wide eG4s mapping datasets generated by G4 ChIP-seq/CUT&Tag, we generate a reference set of genome-wide eG4s across human, mouse, and chicken. Our multi-omics analyses show that most eG4s are identified in one or a few cell types. The eG4s with higher occurrences across samples are more structurally stable, evolutionarily conserved, enriched in promoter regions, mark highly expressed genes, and associate with complex regulatory programs, demonstrating higher confidence level for further functional study. Finally, we integrate millions of functional genomic variants and prioritize eG4s with regulatory functions in disease and cancer context. These efforts have culminated in the comprehensive and interactive database of experimentally validated DNA eG4s. As such, EndoQuad enables users to easily access, download, and repurpose these data for their own research. EndoQuad will become a one-stop resource for eG4 research and lays the foundation for future functional study.

Qian SH, Shi MW, Xiong YL, et al. EndoQuad: a comprehensive genome-wide experimentally validated endogenous G-quadruplex database. Nucleic Acids Research, 2023: gkad966, https://doi.org/10.1093/nar/gkad966.