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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...
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/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. |
format | Online Article Text |
id | pubmed-8716063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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