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In transcriptomics in particular, long reads offer the possibility of sequencing full-length isoforms, which can vastly simplify the identification of novel transcripts and transcript quantification. However, despite this promise, the focus of much long-read method development to date has been on transcript identification, with comparatively little attention paid to quantification. Yet, due to differences in the underlying protocols and technologies, lower throughput (i.e. fewer reads sequenced per sample compared to short-read technologies), as well as technical artifacts, long-read quantification remains a challenge, motivating the continued development and assessment of quantification methods tailored to this increasingly prevalent type of data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We introduce a new method and corresponding user-friendly software tool for long-read transcript quantification called oarfish. Our model incorporates a novel coverage score, which affects the conditional probability of fragment assignment in the underlying probabilistic model. We demonstrate, in both simulated and experimental data, that by accounting for this coverage information, oarfish is able to produce more accurate quantification estimates than existing long-read quantification tools.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>oarfish is implemented in the Rust programming language and is made available as free and open-source software under the BSD 3-clause license. The source code is available at https:\/\/www.github.com\/COMBINE-lab\/oarfish.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf240","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T13:02:30Z","timestamp":1752584550000},"page":"i304-i313","source":"Crossref","is-referenced-by-count":19,"title":["<tt>Oarfish<\/tt>: enhanced probabilistic modeling leads to improved accuracy in long read transcriptome quantification"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6877-4934","authenticated-orcid":false,"given":"Zahra","family":"Zare Jousheghani","sequence":"first","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of Maryland , College Park, MD 20742,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3721-2157","authenticated-orcid":false,"given":"Noor Pratap","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Maryland , College Park, MD 20742,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8463-1675","authenticated-orcid":false,"given":"Rob","family":"Patro","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Maryland , College Park, MD 20742,","place":["United States"]}]}],"member":"286","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"2025071509022759400_btaf240-B1","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41587-023-01815-7","article-title":"High-throughput RNA isoform sequencing using programmed cDNA concatenation","volume":"42","author":"Al\u2019Khafaji","year":"2023","journal-title":"Nat Biotechnol"},{"key":"2025071509022759400_btaf240-B2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13059-020-1935-5","article-title":"Opportunities and 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