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De novo mutational signature discovery in tumor genomes using SparseSignatures
Cancer is the result of mutagenic processes that can be inferred from tumor genomes by analyzing rate spectra of point mutations, or “mutational signatures”. Here we present SparseSignatures, a novel framework to extract signatures from somatic point mutation data. Our approach incorporates a user-s...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270462/ https://www.ncbi.nlm.nih.gov/pubmed/34181655 http://dx.doi.org/10.1371/journal.pcbi.1009119 |
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author | Lal, Avantika Liu, Keli Tibshirani, Robert Sidow, Arend Ramazzotti, Daniele |
author_facet | Lal, Avantika Liu, Keli Tibshirani, Robert Sidow, Arend Ramazzotti, Daniele |
author_sort | Lal, Avantika |
collection | PubMed |
description | Cancer is the result of mutagenic processes that can be inferred from tumor genomes by analyzing rate spectra of point mutations, or “mutational signatures”. Here we present SparseSignatures, a novel framework to extract signatures from somatic point mutation data. Our approach incorporates a user-specified background signature, employs regularization to reduce noise in non-background signatures, uses cross-validation to identify the number of signatures, and is scalable to large datasets. We show that SparseSignatures outperforms current state-of-the-art methods on simulated data using a variety of standard metrics. We then apply SparseSignatures to whole genome sequences of pancreatic and breast tumors, discovering well-differentiated signatures that are linked to known mutagenic mechanisms and are strongly associated with patient clinical features. |
format | Online Article Text |
id | pubmed-8270462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82704622021-07-21 De novo mutational signature discovery in tumor genomes using SparseSignatures Lal, Avantika Liu, Keli Tibshirani, Robert Sidow, Arend Ramazzotti, Daniele PLoS Comput Biol Research Article Cancer is the result of mutagenic processes that can be inferred from tumor genomes by analyzing rate spectra of point mutations, or “mutational signatures”. Here we present SparseSignatures, a novel framework to extract signatures from somatic point mutation data. Our approach incorporates a user-specified background signature, employs regularization to reduce noise in non-background signatures, uses cross-validation to identify the number of signatures, and is scalable to large datasets. We show that SparseSignatures outperforms current state-of-the-art methods on simulated data using a variety of standard metrics. We then apply SparseSignatures to whole genome sequences of pancreatic and breast tumors, discovering well-differentiated signatures that are linked to known mutagenic mechanisms and are strongly associated with patient clinical features. Public Library of Science 2021-06-28 /pmc/articles/PMC8270462/ /pubmed/34181655 http://dx.doi.org/10.1371/journal.pcbi.1009119 Text en © 2021 Lal et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lal, Avantika Liu, Keli Tibshirani, Robert Sidow, Arend Ramazzotti, Daniele De novo mutational signature discovery in tumor genomes using SparseSignatures |
title | De novo mutational signature discovery in tumor genomes using SparseSignatures |
title_full | De novo mutational signature discovery in tumor genomes using SparseSignatures |
title_fullStr | De novo mutational signature discovery in tumor genomes using SparseSignatures |
title_full_unstemmed | De novo mutational signature discovery in tumor genomes using SparseSignatures |
title_short | De novo mutational signature discovery in tumor genomes using SparseSignatures |
title_sort | de novo mutational signature discovery in tumor genomes using sparsesignatures |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270462/ https://www.ncbi.nlm.nih.gov/pubmed/34181655 http://dx.doi.org/10.1371/journal.pcbi.1009119 |
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