RT Journal Article T1 Enhancing R-loop prediction with high-throughput sequencing data A1 Vanhaeren, Thomas A1 Cataneo, Ludovica A1 Divina, Federico A1 Martínez-García, Pedro Manuel K1 Machine learning K1 Gene expression K1 R-loops AB R-loops are three-stranded RNA and DNA hybrid structures that often occur in the genome and play important roles in a variety of cellular processes from bacteria to mammals. Sequencing methods profiling R-loops genome-wide have revealed that they can form co-transcriptionally at cell type specific genes and associate with specific chromatin states during cell differentiation and reprogramming. However, current computational methods for the prediction of R-loops rely solely on their DNA sequence properties, which precludes detection across cell types, tissues or developmental stages. Here, we conduct a machine learning approach that allows the prediction of mammalian cell type-specific R-loops using sequence information and high-throughput sequencing signals. Our predictive models are induced from human samples and achieve highly accurate predictions, with transcriptomics, DNA features, chromatin accessibility and the active gene body H3K36me3 epigenomic mark being the most informative datasets. We generate de novo virtual R-loop maps that show high concordance with experimental ones and capture cell type specificity. Our approach compares favorably to sequence-based methods and can be generalized to mouse datasets. Based on this, we generate virtual R-loop maps in 51 mammalian systems that are freely accessible to the scientific community. PB Oxford Academic YR 2025 FD 2025-06 LK https://hdl.handle.net/10433/24834 UL https://hdl.handle.net/10433/24834 LA en NO NAR Genomics and Bioinformatics, Volume 7, Issue 2, June 2025, lqaf077, https://doi.org/10.1093/nargab/lqaf077 NO Proyecto de investigación:TED2021-131311B-C22 NO Departamento de Deporte e Informática DS RIO RD May 6, 2026