{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:30:29Z","timestamp":1790364629216,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research UK Grand Challenge Award","award":["C98\/A24032"],"award-info":[{"award-number":["C98\/A24032"]}]},{"name":"US National Institute of Health","award":["R01ES030993-01A1"],"award-info":[{"award-number":["R01ES030993-01A1"]}]},{"name":"US National Institute of Health","award":["R01ES032547"],"award-info":[{"award-number":["R01ES032547"]}]},{"name":"Packard Fellowship for Science and Engineering"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Clustered mutations are found in the human germline as well as in the genomes of cancer and normal somatic cells. Clustered events can be imprinted by a multitude of mutational processes, and they have been implicated in both cancer evolution and development disorders. Existing tools for identifying clustered mutations have been optimized for a particular subtype of clustered event and, in most cases, relied on a predefined inter-mutational distance (IMD) cutoff combined with a piecewise linear regression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we present SigProfilerClusters, an automated tool for detecting all types of clustered mutations by calculating a sample-dependent IMD threshold using a simulated background model that takes into account extended sequence context, transcriptional strand asymmetries and regional mutation densities. SigProfilerClusters disentangles all types of clustered events from non-clustered mutations and annotates each clustered event into an established subclass, including the widely used classes of doublet-base substitutions, multi-base substitutions, omikli and kataegis. SigProfilerClusters outputs non-clustered mutations and clustered events using standard data formats as well as provides multiple visualizations for exploring the distributions and patterns of clustered mutations across the genome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>SigProfilerClusters is supported across most operating systems and made freely available at https:\/\/github.com\/AlexandrovLab\/SigProfilerClusters with an extensive documentation located at https:\/\/osf.io\/qpmzw\/wiki\/home\/.<\/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\/btac335","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T19:36:25Z","timestamp":1653075385000},"page":"3470-3473","source":"Crossref","is-referenced-by-count":36,"title":["Examining clustered somatic mutations with SigProfilerClusters"],"prefix":"10.1093","volume":"38","author":[{"given":"Erik N","family":"Bergstrom","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Department of Bioengineering, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Moores Cancer Center, UC San Diego , La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mousumy","family":"Kundu","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Department of Bioengineering, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Moores Cancer Center, UC San Diego , La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-8148","authenticated-orcid":false,"given":"Noura","family":"Tbeileh","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Department of Bioengineering, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Moores Cancer Center, UC San Diego , La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-4515","authenticated-orcid":false,"given":"Ludmil B","family":"Alexandrov","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Department of Bioengineering, UC San Diego , La Jolla, CA 92093, USA"},{"name":"Moores Cancer Center, UC San Diego , La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"2023041407594192600_","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"2023041407594192600_","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"2023041407594192600_","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s12859-020-03772-3","article-title":"Generating realistic null hypothesis of cancer mutational landscapes using SigProfilerSimulator","volume":"21","author":"Bergstrom","year":"2020","journal-title":"BMC Bioinformatics"},{"key":"2023041407594192600_","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1186\/s12864-019-6041-2","article-title":"SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events","volume":"20","author":"Bergstrom","year":"2019","journal-title":"BMC Genomics"},{"key":"2023041407594192600_","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41586-022-04398-6","article-title":"Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA","volume":"602","author":"Bergstrom","year":"2022","journal-title":"Nature"},{"key":"2023041407594192600_","doi-asserted-by":"crossref","first-page":"e1284719","DOI":"10.1080\/2162402X.2017.1284719","article-title":"High expression of PD-1 ligands is associated with kataegis mutational signature and APOBEC3 alterations","volume":"6","author":"Boichard","year":"2017","journal-title":"Oncoimmunology"},{"key":"2023041407594192600_","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/php.12377","article-title":"UV signature mutations","volume":"91","author":"Brash","year":"2015","journal-title":"Photochem. 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