TY - JOUR 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 Y1 - 2025/11/01 JF - Genome Research JO - Genome Research SP - 2578 EP - 2600 DO - 10.1101/gr.279790.124 VL - 35 IS - 11 UR - http://genome.cshlp.org/content/35/11/2578.abstract N2 - 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. ER -