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In this paper, we conduct an unbiased benchmarking of 11 state-of-the-art computational tools as well as traditional tools such as ScanProsite, BLAST, and HMMER for identifying DBPs. We highlight the data leakage issue in conventional datasets leading to inflated performance. We introduce new evaluation datasets to support further development. Through a comprehensive evaluation pipeline, we identify potential limitations in models, feature extraction techniques, and training methods, and recommend solutions regarding these issues. We show that combining the predictions of the two best computational tools with BLAST-based prediction significantly enhances DBP identification capability. We provide this consensus method as user-friendly software. The datasets and software are available at https:\/\/github.com\/Rafeed-bot\/DNA_BP_Benchmarking.<\/jats:p>","DOI":"10.1093\/bib\/bbae634","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T22:51:04Z","timestamp":1733871064000},"source":"Crossref","is-referenced-by-count":5,"title":["Benchmarking recent computational tools for DNA-binding protein identification"],"prefix":"10.1093","volume":"26","author":[{"given":"Xizi","family":"Luo","sequence":"first","affiliation":[{"name":"School of Computing, National University of Singapore , Singapore 119077 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amadeus Song Yi","family":"Chi","sequence":"additional","affiliation":[{"name":"School of Computing, National University of Singapore , Singapore 119077 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre Huikai","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Computing, National University of Singapore , Singapore 119077 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze Jet","family":"Ong","sequence":"additional","affiliation":[{"name":"School of Computing, National University of Singapore , Singapore 119077 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limsoon","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Computing, National University of Singapore , Singapore 119077 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chowdhury Rafeed","family":"Rahman","sequence":"additional","affiliation":[{"name":"School of Computing, National University of Singapore , Singapore 119077 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