{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T09:28:36Z","timestamp":1769851716527,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012669","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS\/NIGMS#2054347"],"award-info":[{"award-number":["DMS\/NIGMS#2054347"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS\/NIGMS#2054321"],"award-info":[{"award-number":["DMS\/NIGMS#2054321"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS#1817156"],"award-info":[{"award-number":["DMS#1817156"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CCF#2107267"],"award-info":[{"award-number":["CCF#2107267"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"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\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS#1764406"],"award-info":[{"award-number":["DMS#1764406"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["594594"],"award-info":[{"award-number":["594594"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>R-loops are a class of non-canonical nucleic acid structures that typically form during transcription when the nascent RNA hybridizes the DNA template strand, leaving the non-template DNA strand unpaired. These structures are abundant in nature and play important physiological and pathological roles. Recent research shows that DNA sequence and topology affect R-loops, yet it remains unclear how these and other factors contribute to R-loop formation. In this work, we investigate the link between nascent RNA folding and the formation of R-loops. We introduce tree-polynomials, a new class of representations of RNA secondary structures. A tree-polynomial representation consists of a rooted tree associated with an RNA secondary structure together with a polynomial that is uniquely identified with the rooted tree. Tree-polynomials enable accurate, interpretable and efficient data analysis of RNA secondary structures without pseudoknots. We develop a computational pipeline for investigating and predicting R-loop formation from a genomic sequence. The pipeline obtains nascent RNA secondary structures from a co-transcriptional RNA folding software, and computes the tree-polynomial representations of the structures. By applying this pipeline to plasmid sequences that contain R-loop forming genes, we establish a strong correlation between the coefficient sums of tree-polynomials and the experimental probability of R-loop formation. Such strong correlation indicates that the pipeline can be used for accurate R-loop prediction. Furthermore, the interpretability of tree-polynomials allows us to characterize the features of RNA secondary structure associated with R-loop formation. In particular, we identify that branches with short stems separated by bulges and interior loops are associated with R-loops.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012669","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T18:38:33Z","timestamp":1734115113000},"page":"e1012669","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tree polynomials identify a link between co-transcriptional R-loops and nascent RNA 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