RT Journal A1 Chantzi, Nikol A1 Nayak, Akshatha A1 Baltoumas, Fotis A. A1 Aplakidou, Eleni A1 Liew, Shiau Wei A1 Galuh, Jesslyn Elvaretta A1 Patsakis, Michail A1 Montgomery, Austin A1 Moeckel, Camille A1 Mouratidis, Ioannis A1 Sazed, Saiful Arefeen A1 Guiblet, Wilfried A1 Karmiris-ObrataƄski, Panagiotis A1 Wang, Guliang A1 Zaravinos, Apostolos A1 Vasquez, Karen M. A1 Kwok, Chun Kit A1 Pavlopoulos, Georgios A. A1 Georgakopoulos-Soares, Ilias T1 Quadrupia provides a comprehensive catalog of G-quadruplexes across genomes from the tree of life JF Genome Research JO Genome Research YR 2025 FD November 01 VO 35 IS 11 SP 2578 OP 2600 DO 10.1101/gr.279790.124 UL http://genome.cshlp.org/content/35/11/2578.abstract AB G-quadruplex DNA structures exhibit a profound influence on essential biological processes, including transcription, replication, telomere maintenance, and genomic stability. These structures have demonstrably shaped organismal evolution. However, a comprehensive, organism-wide G-quadruplex map encompassing the diversity of life has remained elusive. Here, we introduce Quadrupia, the most extensive and well-characterized G-quadruplex database to date, facilitating the exploration of G-quadruplex structures across the evolutionary spectrum. Quadrupia has identified G-quadruplex sequences in 108,449 reference genomes, with a total of 140,181,277 G-quadruplexes. The database also hosts a collection of 319,784 G-quadruplex clusters of 20 or more members, annotated by taxonomic distributions, multiple sequence alignments, profile hidden Markov models, and cross-references to G-quadruplex 3D structures. Examination of G-quadruplexes across functional genomic elements in different taxa indicates preferential orientation and positioning, with significant differences between individual taxonomic groups. For example, we find that G-quadruplexes in bacteria with a single replication origin display profound preference for the leading orientation. Finally, we experimentally validate the most frequently observed G-quadruplexes using CD-spectroscopy, UV melting, and fluorescent-based approaches.