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Systematic noise in sequencing and array data present a significant challenge to the inference of SCNAs for cancer genome analyses. As part of The Cancer Genome Atlas, the Broad Institute Genome Characterization Center developed the Tangent normalization method to generate copy-number profiles using data from single-nucleotide polymorphism (SNP) arrays and whole-exome sequencing (WES) technologies for over 10\u00a0000 pairs of tumors and matched normal samples. Here, we describe the Tangent method, which uses a unique linear combination of normal samples as a reference for each tumor sample, to subtract systematic errors that vary across samples. We also describe a modification of Tangent, called Pseudo-Tangent, which enables denoising through comparisons between tumor profiles when few normal samples are available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Tangent normalization substantially increases signal-to-noise ratios (SNRs) compared to conventional normalization methods in both SNP array and WES analyses. Tangent and Pseudo-Tangent normalizations improve the SNR by reducing noise with minimal effect on signal and exceed the contribution of other steps in the analysis such as choice of segmentation algorithm. Tangent and Pseudo-Tangent are broadly applicable and enable more accurate inference of SCNAs from DNA sequencing and array data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Tangent is available at https:\/\/github.com\/broadinstitute\/tangent and as a Docker image (https:\/\/hub.docker.com\/r\/broadinstitute\/tangent). Tangent is also the normalization method for the copy-number pipeline in Genome Analysis Toolkit 4 (GATK4).<\/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\/btac586","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T20:27:38Z","timestamp":1661804858000},"page":"4677-4686","source":"Crossref","is-referenced-by-count":10,"title":["Tangent normalization for somatic copy-number inference in cancer genome analysis"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3143-9270","authenticated-orcid":false,"given":"Galen F","family":"Gao","sequence":"first","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5732-3471","authenticated-orcid":false,"given":"Coyin","family":"Oh","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School , Boston, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Saksena","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davy","family":"Deng","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay C","family":"Westlake","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A","family":"Hill","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Reich","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Medicine, Division of Medical Genetics, University of California, San Diego , La, Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashton C","family":"Berger","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L","family":"Carter","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School , Boston, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Cherniack","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Meyerson","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"},{"name":"Department of Genetics, Harvard Medical School , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Tabak","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rameen","family":"Beroukhim","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"},{"name":"Department of Medicine, Harvard Medical School , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-0753","authenticated-orcid":false,"given":"Gad","family":"Getz","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge, MA, USA"},{"name":"Department of Pathology, Harvard Medical School , Boston, MA, USA"},{"name":"Department of Pathology, Massachusetts General Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"2022101415193808200_btac586-B1","doi-asserted-by":"crossref","first-page":"20007","DOI":"10.1073\/pnas.0710052104","article-title":"Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma","volume":"104","author":"Beroukhim","year":"2007","journal-title":"Proc. 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