Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes
Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers...
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| Veröffentlicht in: | PLoS genetics 2021-05, Vol.17 (5), p.e1009557 |
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| creator | Wang, Shixiang Li, Huimin Song, Minfang Tao, Ziyu Wu, Tao He, Zaoke Zhao, Xiangyu Wu, Kai Liu, Xue-Song |
| description | Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis. |
| doi_str_mv | 10.1371/journal.pgen.1009557 |
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Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. 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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Biology and Life Sciences Biomarkers, Tumor Chromosomes Copy number Copy number variations Datasets Deoxyribonucleic acid DNA DNA Copy Number Variations - genetics DNA damage DNA Mutational Analysis Double-strand break repair Genetic aspects Genome, Human - genetics Genomes Genomic Instability Genomics Health aspects Humans Male Medicine and Health Sciences Metastases Mutagenesis - genetics Mutation Mutation (Biology) Ovarian cancer Patient outcomes Prognosis Proportional Hazards Models Prostate cancer Prostatic Neoplasms - classification Prostatic Neoplasms - diagnosis Prostatic Neoplasms - genetics Quality control Software Survival Analysis Treatment Outcome Tumors |
| title | Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes |
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