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Mapping genome-wide RNA\u2013DNA interactions is possible using a variety of molecular methods, including using bridging oligonucleotides to ligate RNA and DNA in proximity. While molecular methods have progressed, a robust computational method for calling biologically meaningful RNA\u2013DNA interactions from these data is lacking. Herein, we present RADIAnT, a reads-to-interactions pipeline for analyzing RNA\u2013DNA ligation data. RADIAnT calls interactions against a dataset-specific, unified background, which considers RNA binding site\u2013TSS distance and genomic region bias, and outperforms previously proposed methods in the accurate recall of genome-wide RNA\u2013DNA interactions. Accurate RNA\u2013DNA interaction calling enables the analysis of gene regulatory RNAs in dynamic biological contexts. Here, dynamically chromatin-associated RNAs were identified in the physiologically- and pathologically relevant process of endothelial-to-mesenchymal transition. By depleting candidate chromatin-associated lncRNAs, their gene regulatory behavior at bound target genes important to endothelial phenotype maintenance could be validated. These data demonstrate how effective RNA\u2013DNA interaction calling can help to place RNAs at key points in gene regulatory networks governing cellular behavior.<\/jats:p>","DOI":"10.1093\/nar\/gkag304","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T12:19:48Z","timestamp":1774268388000},"source":"Crossref","is-referenced-by-count":1,"title":["Improved RNA\u2013DNA interaction calling suggests RNA-based gene regulation of phenotypic transitions"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8510-657X","authenticated-orcid":false,"given":"Simonida","family":"Zehr","sequence":"first","affiliation":[{"name":"Goethe University Frankfurt, Institute for Cardiovascular Physiology , Theodor-Stern-Kai 7, 60590Frankfurt am Main , Hesse,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner site Rhein-Main , 60590 Frankfurt am Main 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