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Link to original content: https://api.crossref.org/works/10.1093/BIB/BBAB336
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While there are over a dozen computational predictors of the DNA-binding residues, they are DNA-type agnostic and significantly cross-predict residues that interact with other ligands as DNA binding. We leverage a custom-designed machine learning architecture to introduce DNAgenie, first-of-its-kind predictor of residues that interact with A-DNA, B-DNA and single-stranded DNA. DNAgenie uses a comprehensive physiochemical profile extracted from an input protein sequence and implements a two-step refinement process to provide accurate predictions and to minimize the cross-predictions. Comparative tests on an independent test dataset demonstrate that DNAgenie outperforms the current methods that we adapt to predict residue-level interactions with the three DNA types. Further analysis finds that the use of the second (refinement) step leads to a substantial reduction in the cross predictions. Empirical tests show that DNAgenie\u2019s outputs that are converted to coarse-grained protein-level predictions compare favorably against recent tools that predict which DNA-binding proteins interact with double-stranded versus single-stranded DNAs. Moreover, predictions from the sequences of the whole human proteome reveal that the results produced by DNAgenie substantially overlap with the known DNA-binding proteins while also including promising leads for several hundred previously unknown putative DNA binders. These results suggest that DNAgenie is a valuable tool for the sequence-based characterization of protein functions. The DNAgenie\u2019s webserver is available at http:\/\/biomine.cs.vcu.edu\/servers\/DNAgenie\/.<\/jats:p>","DOI":"10.1093\/bib\/bbab336","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T19:12:01Z","timestamp":1627585921000},"source":"Crossref","is-referenced-by-count":17,"title":["DNAgenie: accurate prediction of DNA-type-specific binding residues in protein sequences"],"prefix":"10.1093","volume":"22","author":[{"given":"Jian","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Computer and Information Technology at the Xinyang Normal University, No.237, Nanhu Road, Xinyang 464000, Henan Province, P.R. China"}]},{"given":"Sina","family":"Ghadermarzi","sequence":"additional","affiliation":[{"name":"Department of Computer Science at the Virginia Commonwealth University, 401 West Main Street, Room E4225, Richmond, Virginia 23284, USA"}]},{"given":"Akila","family":"Katuwawala","sequence":"additional","affiliation":[{"name":"Department of Computer Science from the Virginia Commonwealth University, 401 West Main Street, Room E4225, Richmond, Virginia 23284, USA"}]},{"given":"Lukasz","family":"Kurgan","sequence":"additional","affiliation":[{"name":"Department of Computer Science at the Virginia Commonwealth University, 401 West Main Street, Room E4225, Richmond, Virginia 23284, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"issue":"21","key":"2021110815092531200_ref1","doi-asserted-by":"crossref","first-page":"7364","DOI":"10.1093\/nar\/gkq617","article-title":"Genomic repertoires of DNA-binding transcription factors across the tree of 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