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Network-Based Coverage of Mutational Profiles Reveals Cancer Genes
A central goal in cancer genomics is to identify the somatic alterations that underpin tumor initiation and progression. While commonly mutated cancer genes are readily identifiable, those that are rarely mutated across samples are difficult to distinguish from the large numbers of other infrequentl...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997485/ https://www.ncbi.nlm.nih.gov/pubmed/28957656 http://dx.doi.org/10.1016/j.cels.2017.09.003 |
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author | Hristov, Borislav H. Singh, Mona |
author_facet | Hristov, Borislav H. Singh, Mona |
author_sort | Hristov, Borislav H. |
collection | PubMed |
description | A central goal in cancer genomics is to identify the somatic alterations that underpin tumor initiation and progression. While commonly mutated cancer genes are readily identifiable, those that are rarely mutated across samples are difficult to distinguish from the large numbers of other infrequently mutated genes. We introduce a method, nCOP, that considers per-individual mutational profiles within the context of protein-protein interaction networks in order to identify small connected subnetworks of genes that, while not individually frequently mutated, comprise pathways that are altered across (i.e., “cover”) a large fraction of individuals. By analyzing 6,038 samples across 24 different cancer types, we demonstrate that nCOP is highly effective in identifying cancer genes, including those with low mutation frequencies. Overall, our work demonstrates that combining per-individual mutational information with interaction networks is a powerful approach for tackling the mutational heterogeneity observed across cancers. |
format | Online Article Text |
id | pubmed-5997485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-59974852018-09-27 Network-Based Coverage of Mutational Profiles Reveals Cancer Genes Hristov, Borislav H. Singh, Mona Cell Syst Article A central goal in cancer genomics is to identify the somatic alterations that underpin tumor initiation and progression. While commonly mutated cancer genes are readily identifiable, those that are rarely mutated across samples are difficult to distinguish from the large numbers of other infrequently mutated genes. We introduce a method, nCOP, that considers per-individual mutational profiles within the context of protein-protein interaction networks in order to identify small connected subnetworks of genes that, while not individually frequently mutated, comprise pathways that are altered across (i.e., “cover”) a large fraction of individuals. By analyzing 6,038 samples across 24 different cancer types, we demonstrate that nCOP is highly effective in identifying cancer genes, including those with low mutation frequencies. Overall, our work demonstrates that combining per-individual mutational information with interaction networks is a powerful approach for tackling the mutational heterogeneity observed across cancers. 2017-09-27 /pmc/articles/PMC5997485/ /pubmed/28957656 http://dx.doi.org/10.1016/j.cels.2017.09.003 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Hristov, Borislav H. Singh, Mona Network-Based Coverage of Mutational Profiles Reveals Cancer Genes |
title | Network-Based Coverage of Mutational Profiles Reveals Cancer Genes |
title_full | Network-Based Coverage of Mutational Profiles Reveals Cancer Genes |
title_fullStr | Network-Based Coverage of Mutational Profiles Reveals Cancer Genes |
title_full_unstemmed | Network-Based Coverage of Mutational Profiles Reveals Cancer Genes |
title_short | Network-Based Coverage of Mutational Profiles Reveals Cancer Genes |
title_sort | network-based coverage of mutational profiles reveals cancer genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997485/ https://www.ncbi.nlm.nih.gov/pubmed/28957656 http://dx.doi.org/10.1016/j.cels.2017.09.003 |
work_keys_str_mv | AT hristovborislavh networkbasedcoverageofmutationalprofilesrevealscancergenes AT singhmona networkbasedcoverageofmutationalprofilesrevealscancergenes |