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The baseline algorithm is enhanced by machine-learning predictions of active transcription start sites and an adjustment for the typical \u2018shape profile\u2019 of read-counts along a transcription unit. We show that DENR outperforms simple read-count-based methods for estimating gene and isoform abundances, and that transcription of multiple pre-RNA isoforms per gene is widespread, with frequent differences between cell types. In addition, we provide evidence that a majority of human isoform diversity derives from primary transcription rather than from post-transcriptional processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>DENR and nascentRNASim are freely available at https:\/\/github.com\/CshlSiepelLab\/DENR (version v1.0.0) and https:\/\/github.com\/CshlSiepelLab\/nascentRNASim (version v0.3.0).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab582","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T15:48:18Z","timestamp":1628524098000},"page":"4727-4736","source":"Crossref","is-referenced-by-count":7,"title":["Deconvolution of expression for nascent RNA-sequencing data (DENR) highlights pre-RNA isoform diversity in human cells"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-2818","authenticated-orcid":false,"given":"Yixin","family":"Zhao","sequence":"first","affiliation":[{"name":"Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724, USA"}]},{"given":"Noah","family":"Dukler","sequence":"additional","affiliation":[{"name":"Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724, USA"}]},{"given":"Gilad","family":"Barshad","sequence":"additional","affiliation":[{"name":"Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"},{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}]},{"given":"Shushan","family":"Toneyan","sequence":"additional","affiliation":[{"name":"Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724, USA"}]},{"given":"Charles G","family":"Danko","sequence":"additional","affiliation":[{"name":"Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"},{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3557-7219","authenticated-orcid":false,"given":"Adam","family":"Siepel","sequence":"additional","affiliation":[{"name":"Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory , Cold Spring Harbor, NY 11724, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"2023051607144935100_btab582-B1","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1093\/bioinformatics\/btaa011","article-title":"Defining data-driven primary transcript annotations with primaryTranscriptAnnotation in R","volume":"36","author":"Anderson","year":"2020","journal-title":"Bioinformatics"},{"key":"2023051607144935100_btab582-B2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1093\/bioinformatics\/btw599","article-title":"A generative model for the behavior of RNA polymerase","volume":"33","author":"Azofeifa","year":"2017","journal-title":"Bioinformatics"},{"key":"2023051607144935100_btab582-B3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12915-021-00949-x","article-title":"Characterizing RNA stability genome-wide through combined analysis of PRO-seq and RNA-seq data","volume":"19","author":"Blumberg","year":"2021","journal-title":"BMC Biol"},{"key":"2023051607144935100_btab582-B4","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. 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