{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:25:13Z","timestamp":1772173513831,"version":"3.50.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000086","name":"Directorate for Mathematical and Physical Sciences","doi-asserted-by":"publisher","award":["2054347"],"award-info":[{"award-number":["2054347"]}],"id":[{"id":"10.13039\/100000086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000086","name":"Directorate for Mathematical and Physical Sciences","doi-asserted-by":"publisher","award":["DMS-2054321"],"award-info":[{"award-number":["DMS-2054321"]}],"id":[{"id":"10.13039\/100000086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000086","name":"Directorate for Mathematical and Physical Sciences","doi-asserted-by":"publisher","award":["1716987, 1817156"],"award-info":[{"award-number":["1716987, 1817156"]}],"id":[{"id":"10.13039\/100000086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000086","name":"Directorate for Mathematical and Physical Sciences","doi-asserted-by":"publisher","award":["1815832"],"award-info":[{"award-number":["1815832"]}],"id":[{"id":"10.13039\/100000086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000083","name":"Directorate for Computer and Information Science and Engineering","doi-asserted-by":"publisher","award":["CCF-2107267"],"award-info":[{"award-number":["CCF-2107267"]}],"id":[{"id":"10.13039\/100000083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["MP-TSM-00002798"],"award-info":[{"award-number":["MP-TSM-00002798"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["DGECR-2023-00131"],"award-info":[{"award-number":["DGECR-2023-00131"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2023-04722"],"award-info":[{"award-number":["RGPIN-2023-04722"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010318","name":"the University of Manitoba","doi-asserted-by":"crossref","award":["research start-up funds"],"award-info":[{"award-number":["research start-up funds"]}],"id":[{"id":"10.13039\/100010318","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000888","name":"W. M. Keck Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM139549"],"award-info":[{"award-number":["R35 GM139549"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    R-loops are transient three-stranded nucleic acids that form during transcription when the nascent RNA hybridizes with the template DNA, freeing the non-template strand of the DNA. There is growing evidence that R-loops play important roles in physiological processes such as the regulation of gene expression, and that they contribute to chromosomal instability and disease. It is known that R-loop formation is influenced by both the sequence and the topology of the DNA substrate, but many questions remain about how R-loops form and the three-dimensional structures that they adopt. Here we represent an R-loop as a word in a formal grammar, the\n                    <jats:italic>R-loop grammar<\/jats:italic>\n                    . We use the R-loop grammar to predict R-loop formation. We train the R-loop grammar on experimental data obtained by single-molecule R-loop footprinting and sequencing (SMRF-seq). Despite not explicitly encoding topological information, the R-loop grammar accurately predicts R-loop formation on plasmids with varying starting topologies and outperforms previous methods in R-loop prediction.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1013376","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T18:04:54Z","timestamp":1756490694000},"page":"e1013376","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["The R-loop grammar predicts R-loop formation under different topological constraints"],"prefix":"10.1371","volume":"21","author":[{"given":"Margherita Maria","family":"Ferrari","sequence":"first","affiliation":[]},{"given":"Svetlana","family":"Poznanovi\u0107","sequence":"additional","affiliation":[]},{"given":"Manda","family":"Riehl","sequence":"additional","affiliation":[]},{"given":"Jacob","family":"Lusk","sequence":"additional","affiliation":[]},{"given":"Stella","family":"Hartono","sequence":"additional","affiliation":[]},{"given":"Georgina","family":"Gonzalez-Isunza","sequence":"additional","affiliation":[]},{"given":"Fr\u00e9d\u00e9ric","family":"Ch\u00e9din","sequence":"additional","affiliation":[]},{"given":"Mariel","family":"V\u00e1zquez","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0765-9425","authenticated-orcid":true,"given":"Nata\u0161a","family":"Jonoska","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"issue":"11","key":"pcbi.1013376.ref001","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1101\/gad.280834.116","article-title":"S1-DRIP-seq identifies high expression and polyA tracts as major contributors to R-loop formation","volume":"30","author":"L Wahba","year":"2016","journal-title":"Genes Dev."},{"issue":"3","key":"pcbi.1013376.ref002","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jmb.2017.12.016","article-title":"The affinity of the S9.6 antibody for double-stranded RNAs impacts the accurate mapping of R-loops in fission yeast","volume":"430","author":"SR Hartono","year":"2018","journal-title":"J Mol Biol."},{"issue":"1","key":"pcbi.1013376.ref003","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.molcel.2016.05.032","article-title":"Prevalent, dynamic, and conserved R-loop structures associate with specific epigenomic signatures in mammals","volume":"63","author":"LA Sanz","year":"2016","journal-title":"Mol Cell."},{"issue":"6","key":"pcbi.1013376.ref004","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.molcel.2012.01.017","article-title":"R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters","volume":"45","author":"PA Ginno","year":"2012","journal-title":"Mol Cell."},{"issue":"9","key":"pcbi.1013376.ref005","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41477-017-0004-x","article-title":"The R-loop is a common chromatin feature of the Arabidopsis genome","volume":"3","author":"W Xu","year":"2017","journal-title":"Nat Plants."},{"key":"pcbi.1013376.ref006","first-page":"4","article-title":"Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi-Goutieres syndrome","author":"YW Lim","year":"2015","journal-title":"Elife."},{"issue":"3","key":"pcbi.1013376.ref007","article-title":"Permanganate\/S1 nuclease footprinting reveals non-B DNA structures with regulatory potential across a Mammalian genome","volume":"4","author":"F Kouzine","year":"2017","journal-title":"Cell Syst."},{"issue":"7","key":"pcbi.1013376.ref008","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1016\/j.jmb.2020.02.014","article-title":"Ultra-deep coverage single-molecule R-loop footprinting reveals principles of R-loop formation","volume":"432","author":"M Malig","year":"2020","journal-title":"J Mol Biol."},{"issue":"12","key":"pcbi.1013376.ref009","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.tig.2016.10.002","article-title":"Nascent connections: R-loops and chromatin patterning","volume":"32","author":"F Ch\u00e9din","year":"2016","journal-title":"Trends Genet."},{"key":"pcbi.1013376.ref010","doi-asserted-by":"crossref","unstructured":"Hsieh P, Panyutin IG. 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