{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:09:26Z","timestamp":1792037366269,"version":"4.4.0"},"reference-count":92,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genome Res."],"accepted":{"date-parts":[[2026,4,15]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Precise transcription factor (TF) binding to DNA governs gene regulation, yet nucleotide sequence alone often fails to fully capture binding specificity. Although static DNA shape is a recognized determinant of indirect readout, the role of intrinsic conformational flexibility remains underexplored across TF families. Here, we demonstrate that integrating sequence-derived DNA flexibility descriptors into predictive models improves both prediction and mechanistic interpretability of TF\u2013DNA affinity. Across large-scale in vitro data sets encompassing HT-SELEX and protein-binding microarrays for mammalian and\n                    <jats:italic>Drosophila<\/jats:italic>\n                    TFs, flexibility-augmented models consistently outperform sequence-only baselines and complement DNA shape models. Cross-platform analyses further indicate that flexibility features capture structural information that is robust to platform-specific biases. Using a position-resolved interpretation framework, we uncover family-specific \u201cflexibility footprints,\u201d including recurrent hotspots in core motifs and flanks that align with DNA structural deformations from TF\u2013DNA complex structures. Extending to ENCODE ChIP-seq and DNase-seq data, flexibility augmentation improves classification of functional TF binding sites across diverse TFs and cellular contexts. Collectively, these results underscore the insufficiency of sequence-only models and highlight the utility of the flexibility descriptors as an interpretable component of the TF recognition code.\n                  <\/jats:p>","DOI":"10.1101\/gr.281357.125","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:25:23Z","timestamp":1778775923000},"page":"1158-1175","source":"Crossref","is-referenced-by-count":1,"title":["DNA conformational flexibility descriptors improve transcription factor binding prediction across diverse transcription factor families"],"prefix":"10.1101","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8963-4346","authenticated-orcid":false,"given":"Upalabdha","family":"Dey","sequence":"first","affiliation":[{"name":"Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam 784028, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-5051","authenticated-orcid":false,"given":"Venkata Rajesh","family":"Yella","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, Andhra Pradesh 522302, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-8830","authenticated-orcid":false,"given":"Aditya","family":"Kumar","sequence":"additional","affiliation":[{"name":"Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam 784028, India;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2026062308551331000_36.6.1158.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.008"},{"key":"2026062308551331000_36.6.1158.2","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqad097"},{"key":"2026062308551331000_36.6.1158.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2014.01.007"},{"key":"2026062308551331000_36.6.1158.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.04.006"},{"key":"2026062308551331000_36.6.1158.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03052-3"},{"key":"2026062308551331000_36.6.1158.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00877-6"},{"key":"2026062308551331000_36.6.1158.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1044"},{"key":"2026062308551331000_36.6.1158.8","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.1990.10507828"},{"key":"2026062308551331000_36.6.1158.9","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.1992.10508639"},{"key":"2026062308551331000_36.6.1158.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39577-0"},{"key":"2026062308551331000_36.6.1158.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2023.102698"},{"key":"2026062308551331000_36.6.1158.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06661-w"},{"key":"2026062308551331000_36.6.1158.13","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07169.x"},{"key":"2026062308551331000_36.6.1158.14","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.1995.10508842"},{"key":"2026062308551331000_36.6.1158.15","doi-asserted-by":"crossref","unstructured":"Bulyk ML . 2006. 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