{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:00:03Z","timestamp":1780578003089,"version":"3.54.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"18","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA-BC-011566"],"award-info":[{"award-number":["ZIA-BC-011566"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>MicroRNAs (miRNAs) are master regulators of gene expression in cancers. Their sequence variants or isoforms (isomiRs) are highly abundant and possess unique functions. Given their short sequence length and high heterogeneity, mapping isomiRs can be challenging; without adequate depth and data aggregation, low frequency events are often disregarded. To address these challenges, we present the Tumor IsomiR Encyclopedia (TIE): a dynamic database of isomiRs from over 10\u00a0000 adult and pediatric tumor samples in The Cancer Genome Atlas (TCGA) and The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects. A key novelty of TIE is its ability to annotate heterogeneous isomiR sequences and aggregate the variants obtained across all datasets. Results can be browsed online or downloaded as spreadsheets. Here, we show analysis of isomiRs of miR-21 and miR-30a to demonstrate the utility of TIE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>TIE search engine and data are freely available to use at https:\/\/isomir.ccr.cancer.gov\/.<\/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\/btab172","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T16:13:25Z","timestamp":1615824805000},"page":"3023-3025","source":"Crossref","is-referenced-by-count":22,"title":["Tumor IsomiR Encyclopedia (TIE): a pan-cancer database of miRNA isoforms"],"prefix":"10.1093","volume":"37","author":[{"given":"Xavier","family":"Bofill-De Ros","sequence":"first","affiliation":[{"name":"RNA Mediated Gene Regulation Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Luke","sequence":"additional","affiliation":[{"name":"Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research , Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Guthridge","sequence":"additional","affiliation":[{"name":"Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research , Frederick, MD, USA"},{"name":"Leidos Biomedical Research Inc. , Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Mudunuri","sequence":"additional","affiliation":[{"name":"Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research , Frederick, MD, USA"},{"name":"Leidos Biomedical Research Inc. , Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Loss","sequence":"additional","affiliation":[{"name":"Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research , Frederick, MD, USA"},{"name":"Leidos Biomedical Research Inc. , Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-5363","authenticated-orcid":false,"given":"Shuo","family":"Gu","sequence":"additional","affiliation":[{"name":"RNA Mediated Gene Regulation Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"2023061310565616500_btab172-B1","doi-asserted-by":"crossref","first-page":"11467","DOI":"10.1073\/pnas.1317751111","article-title":"PAPD5-mediated 3\u2019 adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease","volume":"111","author":"Boele","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023061310565616500_btab172-B2","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1093\/bioinformatics\/bty843","article-title":"QuagmiR: a cloud-based application for isomiR big data analytics","volume":"35","author":"Bofill-De Ros","year":"2019","journal-title":"Bioinformatics"},{"key":"2023061310565616500_btab172-B3","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrc1840","article-title":"Oncomirs \u2013 microRNAs with a role in cancer","volume":"6","author":"Esquela-Kerscher","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"2023061310565616500_btab172-B4","doi-asserted-by":"crossref","first-page":"D132","DOI":"10.1093\/nar\/gkz885","article-title":"MirGeneDB 2.0: the metazoan microRNA complement","volume":"48","author":"Fromm","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2023061310565616500_btab172-B5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-018-0045-7","article-title":"Regulation of microRNA function in animals","volume":"20","author":"Gebert","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023061310565616500_btab172-B6","doi-asserted-by":"crossref","first-page":"D155","DOI":"10.1093\/nar\/gky1141","article-title":"miRBase: from microRNA sequences to function","volume":"47","author":"Kozomara","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023061310565616500_btab172-B7","doi-asserted-by":"crossref","first-page":"E1106","DOI":"10.1073\/pnas.1420955112","article-title":"Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs","volume":"112","author":"Londin","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023061310565616500_btab172-B8","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1101\/gr.222067.117","article-title":"Toward the human cellular microRNAome","volume":"27","author":"McCall","year":"2017","journal-title":"Genome Res"},{"key":"2023061310565616500_btab172-B9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nature09284","article-title":"OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma","volume":"467","author":"Medina","year":"2010","journal-title":"Nature"},{"key":"2023061310565616500_btab172-B10","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1101\/gr.7179508","article-title":"Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells","volume":"18","author":"Morin","year":"2008","journal-title":"Genome Res"},{"key":"2023061310565616500_btab172-B11","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41420-020-0282-3","article-title":"Expression profiling of microRNAs and isomiRs in conventional central chondrosarcoma","volume":"6","author":"Parafioriti","year":"2020","journal-title":"Cell Death Discov"},{"key":"2023061310565616500_btab172-B12","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tibs.2012.07.002","article-title":"MicroRNA turnover: when, how, and why","volume":"37","author":"R\u00fcegger","year":"2012","journal-title":"Trends Biochem. Sci"},{"key":"2023061310565616500_btab172-B13","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.molcel.2019.01.010","article-title":"The RNase PARN controls the levels of specific miRNAs that contribute to p53 regulation","volume":"73","author":"Shukla","year":"2019","journal-title":"Mol. Cell"},{"key":"2023061310565616500_btab172-B14","doi-asserted-by":"crossref","first-page":"9158","DOI":"10.1093\/nar\/gkv922","article-title":"Beyond the one-locus-one-miRNA paradigm: microRNA isoforms enable deeper insights into breast cancer heterogeneity","volume":"43","author":"Telonis","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023061310565616500_btab172-B15","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1093\/nar\/gkx082","article-title":"Knowledge about the presence or absence of miRNA isoforms (isomiRs) can successfully discriminate amongst 32 TCGA cancer types","volume":"45","author":"Telonis","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2023061310565616500_btab172-B16","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1158\/0008-5472.CAN-17-1947","article-title":"Race disparities in the contribution of miRNA isoforms and tRNA-derived fragments to triple-negative breast cancer","volume":"78","author":"Telonis","year":"2018","journal-title":"Cancer Res"},{"key":"2023061310565616500_btab172-B17","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s12885-019-5340-y","article-title":"Tumor classification and biomarker discovery based on the 5\u2019isomiR expression level","volume":"19","author":"Wang","year":"2019","journal-title":"BMC Cancer"},{"key":"2023061310565616500_btab172-B18","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.molcel.2019.05.014","article-title":"3\u2019 Uridylation confers miRNAs with non-canonical target repertoires","volume":"75","author":"Yang","year":"2019","journal-title":"Mol. Cell"},{"key":"2023061310565616500_btab172-B19","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1038\/s41467-020-16533-w","article-title":"AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2","volume":"11","author":"Yang","year":"2020","journal-title":"Nat. Commun"},{"key":"2023061310565616500_btab172-B20","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1093\/bioinformatics\/btw070","article-title":"IsomiR Bank: a research resource for tracking IsomiRs","volume":"32","author":"Zhang","year":"2016","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btab172\/38620666\/btab172.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/18\/3023\/50579499\/btab172.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/18\/3023\/50579499\/btab172.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T06:59:01Z","timestamp":1686639541000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/18\/3023\/6174685"}},"subtitle":[],"editor":[{"given":"Yann","family":"Ponty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":20,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2021,9,29]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btab172","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.20.259713","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9,15]]},"published":{"date-parts":[[2021,3,17]]}}}