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Identification of TRs is of utmost importance in many biological applications, including but not limited to elucidating biological development mechanisms, identifying key disease genes, and predicting therapeutic targets. Various computational methods based on next-generation sequencing (NGS) data have been developed in the past decade, yet no systematic evaluation of NGS-based methods has been offered. We classified these methods into two categories based on shared characteristics, namely library-based and region-based methods. We further conducted benchmark studies to evaluate the accuracy, sensitivity, coverage, and usability of NGS-based methods with molecular experimental datasets. Results show that BART, ChIP-Atlas, and Lisa have relatively better performance. Besides, we point out the limitations of NGS-based methods and explore potential directions for further improvement.<\/jats:p>","DOI":"10.1093\/bib\/bbae366","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T01:55:54Z","timestamp":1722477354000},"source":"Crossref","is-referenced-by-count":7,"title":["Assessing next-generation sequencing-based computational methods for predicting transcriptional regulators with query gene sets"],"prefix":"10.1093","volume":"25","author":[{"given":"Zeyu","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Statistics and Data Science , Moody School of Graduate and Advanced Studies, , 3225 Daniel Ave., P.O. Box 750332, Dallas, TX, United States"},{"name":"Southern Methodist University , Moody School of Graduate and Advanced Studies, , 3225 Daniel Ave., P.O. Box 750332, Dallas, TX, United States"}]},{"given":"Xue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Peter O\u2019Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center , 5323 Harry Hines Blvd, Dallas, TX, United States"}]},{"given":"Qiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Data Science , College of Science, , 501 S. Nedderman Dr., Arlington, TX 76019, United States"},{"name":"University of Texas at Arlington , College of Science, , 501 S. Nedderman Dr., Arlington, TX 76019, United States"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8561-6511","authenticated-orcid":false,"given":"Xinlei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Data Science , College of Science, , 501 S. Nedderman Dr., Arlington, TX 76019, United States"},{"name":"University of Texas at Arlington , College of Science, , 501 S. Nedderman Dr., Arlington, TX 76019, United States"},{"name":"Department of Mathematics, University of Texas at Arlington , 411 S. Nedderman Dr., Arlington, TX 76019, United States"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5815-4457","authenticated-orcid":false,"given":"Lin","family":"Xu","sequence":"additional","affiliation":[{"name":"Quantitative Biomedical Research Center, Peter O\u2019Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center , 5323 Harry Hines Blvd, Dallas, TX, United States"},{"name":"Department of Pediatrics , Division of Hematology\/Oncology, , 5323 Harry Hines Blvd., Dallas, TX, United States"},{"name":"University of Texas Southwestern Medical Center , Division of Hematology\/Oncology, , 5323 Harry Hines Blvd., Dallas, TX, United States"}]}],"member":"286","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"2024073110361406300_ref1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0022-2836(61)80072-7","article-title":"Genetic regulatory mechanisms in the synthesis of 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