Phylogenetic quantification of intra-tumour heterogeneity.

Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively qua...

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Autores principales:	Roland F Schwarz, Anne Trinh, Botond Sipos, James D Brenton, Nick Goldman, Florian Markowetz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6dd413daf5624a3ca6cb2ee07f8518da
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spelling	oai:doaj.org-article:6dd413daf5624a3ca6cb2ee07f8518da2021-11-18T05:52:58ZPhylogenetic quantification of intra-tumour heterogeneity.1553-734X1553-735810.1371/journal.pcbi.1003535https://doaj.org/article/6dd413daf5624a3ca6cb2ee07f8518da2014-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24743184/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data.Roland F SchwarzAnne TrinhBotond SiposJames D BrentonNick GoldmanFlorian MarkowetzPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 4, p e1003535 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Roland F Schwarz Anne Trinh Botond Sipos James D Brenton Nick Goldman Florian Markowetz Phylogenetic quantification of intra-tumour heterogeneity.
description	Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data.
format	article
author	Roland F Schwarz Anne Trinh Botond Sipos James D Brenton Nick Goldman Florian Markowetz
author_facet	Roland F Schwarz Anne Trinh Botond Sipos James D Brenton Nick Goldman Florian Markowetz
author_sort	Roland F Schwarz
title	Phylogenetic quantification of intra-tumour heterogeneity.
title_short	Phylogenetic quantification of intra-tumour heterogeneity.
title_full	Phylogenetic quantification of intra-tumour heterogeneity.
title_fullStr	Phylogenetic quantification of intra-tumour heterogeneity.
title_full_unstemmed	Phylogenetic quantification of intra-tumour heterogeneity.
title_sort	phylogenetic quantification of intra-tumour heterogeneity.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6dd413daf5624a3ca6cb2ee07f8518da
work_keys_str_mv	AT rolandfschwarz phylogeneticquantificationofintratumourheterogeneity AT annetrinh phylogeneticquantificationofintratumourheterogeneity AT botondsipos phylogeneticquantificationofintratumourheterogeneity AT jamesdbrenton phylogeneticquantificationofintratumourheterogeneity AT nickgoldman phylogeneticquantificationofintratumourheterogeneity AT florianmarkowetz phylogeneticquantificationofintratumourheterogeneity
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Phylogenetic quantification of intra-tumour heterogeneity.

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