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Enhancing cancer clonality analysis with integrative genomics
INTRODUCTION: It is understood that cancer is a clonal disease initiated by a single cell, and that metastasis, which is the spread of cancer from the primary site, is also initiated by a single cell. The seemingly natural capability of cancer to adapt dynamically in a Darwinian manner is a primary...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597064/ https://www.ncbi.nlm.nih.gov/pubmed/26424171 http://dx.doi.org/10.1186/1471-2105-16-S13-S7 |
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author | Peterson, Erich A Bauer, Michael A Chavan, Shweta S Ashby, Cody Weinhold, Niels Heuck, Christoph J Morgan, Gareth J Johann, Donald J |
author_facet | Peterson, Erich A Bauer, Michael A Chavan, Shweta S Ashby, Cody Weinhold, Niels Heuck, Christoph J Morgan, Gareth J Johann, Donald J |
author_sort | Peterson, Erich A |
collection | PubMed |
description | INTRODUCTION: It is understood that cancer is a clonal disease initiated by a single cell, and that metastasis, which is the spread of cancer from the primary site, is also initiated by a single cell. The seemingly natural capability of cancer to adapt dynamically in a Darwinian manner is a primary reason for therapeutic failures. Survival advantages may be induced by cancer therapies and also occur as a result of inherent cell and microenvironmental factors. The selected "more fit" clones outmatch their competition and then become dominant in the tumor via propagation of progeny. This clonal expansion leads to relapse, therapeutic resistance and eventually death. The goal of this study is to develop and demonstrate a more detailed clonality approach by utilizing integrative genomics. METHODS: Patient tumor samples were profiled by Whole Exome Sequencing (WES) and RNA-seq on an Illumina HiSeq 2500 and methylation profiling was performed on the Illumina Infinium 450K array. STAR and the Haplotype Caller were used for RNA-seq processing. Custom approaches were used for the integration of the multi-omic datasets. RESULTS: Reported are major enhancements to CloneViz, which now provides capabilities enabling a formal tumor multi-dimensional clonality analysis by integrating: i) DNA mutations, ii) RNA expressed mutations, and iii) DNA methylation data. RNA and DNA methylation integration were not previously possible, by CloneViz (previous version) or any other clonality method to date. This new approach, named iCloneViz (integrated CloneViz) employs visualization and quantitative methods, revealing an integrative genomic mutational dissection and traceability (DNA, RNA, epigenetics) thru the different layers of molecular structures. CONCLUSION: The iCloneViz approach can be used for analysis of clonal evolution and mutational dynamics of multi-omic data sets. Revealing tumor clonal complexity in an integrative and quantitative manner facilitates improved mutational characterization, understanding, and therapeutic assignments. |
format | Online Article Text |
id | pubmed-4597064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45970642015-10-08 Enhancing cancer clonality analysis with integrative genomics Peterson, Erich A Bauer, Michael A Chavan, Shweta S Ashby, Cody Weinhold, Niels Heuck, Christoph J Morgan, Gareth J Johann, Donald J BMC Bioinformatics Proceedings INTRODUCTION: It is understood that cancer is a clonal disease initiated by a single cell, and that metastasis, which is the spread of cancer from the primary site, is also initiated by a single cell. The seemingly natural capability of cancer to adapt dynamically in a Darwinian manner is a primary reason for therapeutic failures. Survival advantages may be induced by cancer therapies and also occur as a result of inherent cell and microenvironmental factors. The selected "more fit" clones outmatch their competition and then become dominant in the tumor via propagation of progeny. This clonal expansion leads to relapse, therapeutic resistance and eventually death. The goal of this study is to develop and demonstrate a more detailed clonality approach by utilizing integrative genomics. METHODS: Patient tumor samples were profiled by Whole Exome Sequencing (WES) and RNA-seq on an Illumina HiSeq 2500 and methylation profiling was performed on the Illumina Infinium 450K array. STAR and the Haplotype Caller were used for RNA-seq processing. Custom approaches were used for the integration of the multi-omic datasets. RESULTS: Reported are major enhancements to CloneViz, which now provides capabilities enabling a formal tumor multi-dimensional clonality analysis by integrating: i) DNA mutations, ii) RNA expressed mutations, and iii) DNA methylation data. RNA and DNA methylation integration were not previously possible, by CloneViz (previous version) or any other clonality method to date. This new approach, named iCloneViz (integrated CloneViz) employs visualization and quantitative methods, revealing an integrative genomic mutational dissection and traceability (DNA, RNA, epigenetics) thru the different layers of molecular structures. CONCLUSION: The iCloneViz approach can be used for analysis of clonal evolution and mutational dynamics of multi-omic data sets. Revealing tumor clonal complexity in an integrative and quantitative manner facilitates improved mutational characterization, understanding, and therapeutic assignments. BioMed Central 2015-09-25 /pmc/articles/PMC4597064/ /pubmed/26424171 http://dx.doi.org/10.1186/1471-2105-16-S13-S7 Text en Copyright © 2015 Peterson et al. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Proceedings Peterson, Erich A Bauer, Michael A Chavan, Shweta S Ashby, Cody Weinhold, Niels Heuck, Christoph J Morgan, Gareth J Johann, Donald J Enhancing cancer clonality analysis with integrative genomics |
title | Enhancing cancer clonality analysis with integrative genomics |
title_full | Enhancing cancer clonality analysis with integrative genomics |
title_fullStr | Enhancing cancer clonality analysis with integrative genomics |
title_full_unstemmed | Enhancing cancer clonality analysis with integrative genomics |
title_short | Enhancing cancer clonality analysis with integrative genomics |
title_sort | enhancing cancer clonality analysis with integrative genomics |
topic | Proceedings |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597064/ https://www.ncbi.nlm.nih.gov/pubmed/26424171 http://dx.doi.org/10.1186/1471-2105-16-S13-S7 |
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