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Statistical tests for intra-tumour clonal co-occurrence and exclusivity

Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in...

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Autores principales: Kuipers, Jack, Moore, Ariane L., Jahn, Katharina, Schraml, Peter, Wang, Feng, Morita, Kiyomi, Futreal, P. Andrew, Takahashi, Koichi, Beisel, Christian, Moch, Holger, Beerenwinkel, Niko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716063/
https://www.ncbi.nlm.nih.gov/pubmed/34910733
http://dx.doi.org/10.1371/journal.pcbi.1009036
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author Kuipers, Jack
Moore, Ariane L.
Jahn, Katharina
Schraml, Peter
Wang, Feng
Morita, Kiyomi
Futreal, P. Andrew
Takahashi, Koichi
Beisel, Christian
Moch, Holger
Beerenwinkel, Niko
author_facet Kuipers, Jack
Moore, Ariane L.
Jahn, Katharina
Schraml, Peter
Wang, Feng
Morita, Kiyomi
Futreal, P. Andrew
Takahashi, Koichi
Beisel, Christian
Moch, Holger
Beerenwinkel, Niko
author_sort Kuipers, Jack
collection PubMed
description Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in a co-occurring or clonally exclusive fashion over a cohort of patient samples may be suggestive of a synergistic effect between the different clones carrying these mutations. We therefore developed a novel statistical testing framework, called GeneAccord, to identify such gene pairs that are altered in distinct subclones of the same tumour. We analysed our framework for calibration and power. By comparing its performance to baseline methods, we demonstrate that to control type I errors, it is essential to account for the evolutionary dependencies among clones. In applying GeneAccord to the single-cell sequencing of a cohort of 123 acute myeloid leukaemia patients, we find 1 clonally co-occurring and 8 clonally exclusive gene pairs. The clonally exclusive pairs mostly involve genes of the key signalling pathways.
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spelling pubmed-87160632021-12-30 Statistical tests for intra-tumour clonal co-occurrence and exclusivity Kuipers, Jack Moore, Ariane L. Jahn, Katharina Schraml, Peter Wang, Feng Morita, Kiyomi Futreal, P. Andrew Takahashi, Koichi Beisel, Christian Moch, Holger Beerenwinkel, Niko PLoS Comput Biol Research Article Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in a co-occurring or clonally exclusive fashion over a cohort of patient samples may be suggestive of a synergistic effect between the different clones carrying these mutations. We therefore developed a novel statistical testing framework, called GeneAccord, to identify such gene pairs that are altered in distinct subclones of the same tumour. We analysed our framework for calibration and power. By comparing its performance to baseline methods, we demonstrate that to control type I errors, it is essential to account for the evolutionary dependencies among clones. In applying GeneAccord to the single-cell sequencing of a cohort of 123 acute myeloid leukaemia patients, we find 1 clonally co-occurring and 8 clonally exclusive gene pairs. The clonally exclusive pairs mostly involve genes of the key signalling pathways. Public Library of Science 2021-12-15 /pmc/articles/PMC8716063/ /pubmed/34910733 http://dx.doi.org/10.1371/journal.pcbi.1009036 Text en © 2021 Kuipers 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
Kuipers, Jack
Moore, Ariane L.
Jahn, Katharina
Schraml, Peter
Wang, Feng
Morita, Kiyomi
Futreal, P. Andrew
Takahashi, Koichi
Beisel, Christian
Moch, Holger
Beerenwinkel, Niko
Statistical tests for intra-tumour clonal co-occurrence and exclusivity
title Statistical tests for intra-tumour clonal co-occurrence and exclusivity
title_full Statistical tests for intra-tumour clonal co-occurrence and exclusivity
title_fullStr Statistical tests for intra-tumour clonal co-occurrence and exclusivity
title_full_unstemmed Statistical tests for intra-tumour clonal co-occurrence and exclusivity
title_short Statistical tests for intra-tumour clonal co-occurrence and exclusivity
title_sort statistical tests for intra-tumour clonal co-occurrence and exclusivity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716063/
https://www.ncbi.nlm.nih.gov/pubmed/34910733
http://dx.doi.org/10.1371/journal.pcbi.1009036
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