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Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples
BACKGROUND: The use of a personalized haplotype-specific genome assembly, rather than an unrelated, mosaic genome like GRCh38, as a reference for detecting the full spectrum of somatic events from cancers has long been advocated but has never been explored in tumor-normal paired samples. Here, we pr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648002/ https://www.ncbi.nlm.nih.gov/pubmed/36352452 http://dx.doi.org/10.1186/s13059-022-02803-x |
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author | Xiao, Chunlin Chen, Zhong Chen, Wanqiu Padilla, Cory Colgan, Michael Wu, Wenjun Fang, Li-Tai Liu, Tiantian Yang, Yibin Schneider, Valerie Wang, Charles Xiao, Wenming |
author_facet | Xiao, Chunlin Chen, Zhong Chen, Wanqiu Padilla, Cory Colgan, Michael Wu, Wenjun Fang, Li-Tai Liu, Tiantian Yang, Yibin Schneider, Valerie Wang, Charles Xiao, Wenming |
author_sort | Xiao, Chunlin |
collection | PubMed |
description | BACKGROUND: The use of a personalized haplotype-specific genome assembly, rather than an unrelated, mosaic genome like GRCh38, as a reference for detecting the full spectrum of somatic events from cancers has long been advocated but has never been explored in tumor-normal paired samples. Here, we provide the first demonstrated use of de novo assembled personalized genome as a reference for cancer mutation detection and quantifying the effects of the reference genomes on the accuracy of somatic mutation detection. RESULTS: We generate de novo assemblies of the first tumor-normal paired genomes, both nuclear and mitochondrial, derived from the same individual with triple negative breast cancer. The personalized genome was chromosomal scale, haplotype phased, and annotated. We demonstrate that it provides individual specific haplotypes for complex regions and medically relevant genes. We illustrate that the personalized genome reference not only improves read alignments for both short-read and long-read sequencing data but also ameliorates the detection accuracy of somatic SNVs and SVs. We identify the equivalent somatic mutation calls between two genome references and uncover novel somatic mutations only when personalized genome assembly is used as a reference. CONCLUSIONS: Our findings demonstrate that use of a personalized genome with individual-specific haplotypes is essential for accurate detection of the full spectrum of somatic mutations in the paired tumor-normal samples. The unique resource and methodology established in this study will be beneficial to the development of precision oncology medicine not only for breast cancer, but also for other cancers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02803-x. |
format | Online Article Text |
id | pubmed-9648002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-96480022022-11-15 Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples Xiao, Chunlin Chen, Zhong Chen, Wanqiu Padilla, Cory Colgan, Michael Wu, Wenjun Fang, Li-Tai Liu, Tiantian Yang, Yibin Schneider, Valerie Wang, Charles Xiao, Wenming Genome Biol Research BACKGROUND: The use of a personalized haplotype-specific genome assembly, rather than an unrelated, mosaic genome like GRCh38, as a reference for detecting the full spectrum of somatic events from cancers has long been advocated but has never been explored in tumor-normal paired samples. Here, we provide the first demonstrated use of de novo assembled personalized genome as a reference for cancer mutation detection and quantifying the effects of the reference genomes on the accuracy of somatic mutation detection. RESULTS: We generate de novo assemblies of the first tumor-normal paired genomes, both nuclear and mitochondrial, derived from the same individual with triple negative breast cancer. The personalized genome was chromosomal scale, haplotype phased, and annotated. We demonstrate that it provides individual specific haplotypes for complex regions and medically relevant genes. We illustrate that the personalized genome reference not only improves read alignments for both short-read and long-read sequencing data but also ameliorates the detection accuracy of somatic SNVs and SVs. We identify the equivalent somatic mutation calls between two genome references and uncover novel somatic mutations only when personalized genome assembly is used as a reference. CONCLUSIONS: Our findings demonstrate that use of a personalized genome with individual-specific haplotypes is essential for accurate detection of the full spectrum of somatic mutations in the paired tumor-normal samples. The unique resource and methodology established in this study will be beneficial to the development of precision oncology medicine not only for breast cancer, but also for other cancers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02803-x. BioMed Central 2022-11-09 /pmc/articles/PMC9648002/ /pubmed/36352452 http://dx.doi.org/10.1186/s13059-022-02803-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xiao, Chunlin Chen, Zhong Chen, Wanqiu Padilla, Cory Colgan, Michael Wu, Wenjun Fang, Li-Tai Liu, Tiantian Yang, Yibin Schneider, Valerie Wang, Charles Xiao, Wenming Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples |
title | Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples |
title_full | Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples |
title_fullStr | Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples |
title_full_unstemmed | Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples |
title_short | Personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples |
title_sort | personalized genome assembly for accurate cancer somatic mutation discovery using tumor-normal paired reference samples |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648002/ https://www.ncbi.nlm.nih.gov/pubmed/36352452 http://dx.doi.org/10.1186/s13059-022-02803-x |
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