{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:24:55Z","timestamp":1772609095380,"version":"3.50.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["1145912"],"award-info":[{"award-number":["1145912"]}]},{"name":"Independent Research Institutes Infrastructure","award":["9000220"],"award-info":[{"award-number":["9000220"]}]},{"DOI":"10.13039\/501100000951","name":"Cancer Council Victoria","doi-asserted-by":"publisher","award":["1124178"],"award-info":[{"award-number":["1124178"]}],"id":[{"id":"10.13039\/501100000951","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Victorian State Government Operational Infrastructure Support"},{"name":"Victorian Cancer Agency fellowship","award":["MCRF15018"],"award-info":[{"award-number":["MCRF15018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Calling copy number alterations (CNAs) from RNA sequencing (RNA-Seq) is challenging, because of the marked variability in coverage across genes and paucity of single nucleotide polymorphisms (SNPs). We have adapted SuperFreq to call absolute and allele sensitive CNAs from RNA-Seq. SuperFreq uses an error-propagation framework to combine and maximize information from read counts and B-allele frequencies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We used datasets from The Cancer Genome Atlas (TCGA) to assess the validity of CNA calls from RNA-Seq. When ploidy estimates were consistent, we found agreement with DNA SNP-arrays for over 98% of the genome for acute myeloid leukaemia (TCGA-AML, n\u2009=\u2009116) and 87% for colorectal cancer (TCGA-CRC, n\u2009=\u2009377). The sensitivity of CNA calling from RNA-Seq was dependent on gene density. Using RNA-Seq, SuperFreq detected 78% of CNA calls covering 100 or more genes with a precision of 94%. Recall dropped for focal events, but this also depended on signal intensity. For example, in the CRC cohort SuperFreq identified all cases (7\/7) with high-level amplification of ERBB2, where the copy number was typically &amp;gt;20, but identified only 6% of cases (1\/17) with moderate amplification of IGF2, which occurs over a smaller interval. SuperFreq offers an integrated platform for identification of CNAs and point mutations. As evidence of how SuperFreq can be applied, we used it to reproduce the established relationship between somatic mutation load and CNA profile in CRC using RNA-Seq alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>SuperFreq is implemented in R and the code is available through GitHub: https:\/\/github.com\/ChristofferFlensburg\/SuperFreq\/. Data and code to reproduce the figures are available at: https:\/\/gitlab.wehi.edu.au\/flensburg.c\/SuperFreq_RNA_paper. Data from TCGA (phs000178) was accessed from GDC following completion of a data access request through the database of Genotypes and Phenotypes (dbGaP). Data from the Leucegene consortium was downloaded from GEO (AML samples: GSE67040; normal CD34+ cells: GSE48846).<\/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\/btab440","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T07:09:41Z","timestamp":1623740981000},"page":"4023-4032","source":"Crossref","is-referenced-by-count":13,"title":["Detecting copy number alterations in RNA-Seq using SuperFreq"],"prefix":"10.1093","volume":"37","author":[{"given":"Christoffer","family":"Flensburg","sequence":"first","affiliation":[{"name":"Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research , Parkville, VIC 3052, Australia"},{"name":"Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne , Parkville, VIC 3010, Australia"}]},{"given":"Alicia","family":"Oshlack","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre , Melbourne, VIC 3000, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne , Parkville, VIC 3010, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6087-635X","authenticated-orcid":false,"given":"Ian J","family":"Majewski","sequence":"additional","affiliation":[{"name":"Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research , Parkville, VIC 3052, Australia"},{"name":"Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne , Parkville, VIC 3010, Australia"}]}],"member":"286","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"2023051607122805600_btab440-B1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"},{"key":"2023051607122805600_btab440-B2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature11252","article-title":"Comprehensive molecular characterization of human colon and rectal cancer","volume":"487","year":"2012","journal-title":"Nature"},{"key":"2023051607122805600_btab440-B3","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1056\/NEJMoa1301689","article-title":"Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia","volume":"368","year":"2013","journal-title":"N. 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