Cargando…

polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance

BACKGROUND: To ensure cancer patients are stratified towards treatments that are optimally beneficial, it is a priority to define robust molecular subtypes using clustering methods applied to high-dimensional biological data. If each of these methods produces different numbers of clusters for the sa...

Descripción completa

Detalles Bibliográficos
Autores principales: Eason, Katherine, Nyamundanda, Gift, Sadanandam, Anguraj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970540/
https://www.ncbi.nlm.nih.gov/pubmed/29801433
http://dx.doi.org/10.1186/s12859-018-2204-4
_version_ 1783326152232796160
author Eason, Katherine
Nyamundanda, Gift
Sadanandam, Anguraj
author_facet Eason, Katherine
Nyamundanda, Gift
Sadanandam, Anguraj
author_sort Eason, Katherine
collection PubMed
description BACKGROUND: To ensure cancer patients are stratified towards treatments that are optimally beneficial, it is a priority to define robust molecular subtypes using clustering methods applied to high-dimensional biological data. If each of these methods produces different numbers of clusters for the same data, it is difficult to achieve an optimal solution. Here, we introduce “polyClustR”, a tool that reconciles clusters identified by different methods into subtype “communities” using a hypergeometric test or a measure of relative proportion of common samples. RESULTS: The polyClustR pipeline was initially tested using a breast cancer dataset to demonstrate how results are compatible with and add to the understanding of this well-characterised cancer. Two uveal melanoma datasets were then utilised to identify and validate novel subtype communities with significant metastasis-free prognostic differences and associations with known chromosomal aberrations. CONCLUSION: We demonstrate the value of the polyClustR approach of applying multiple consensus clustering algorithms and systematically reconciling the results in identifying novel subtype communities of two cancer types, which nevertheless are compatible with established understanding of these diseases. An R implementation of the pipeline is available at: https://github.com/syspremed/polyClustR ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2204-4) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5970540
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-59705402018-05-30 polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance Eason, Katherine Nyamundanda, Gift Sadanandam, Anguraj BMC Bioinformatics Methodology Article BACKGROUND: To ensure cancer patients are stratified towards treatments that are optimally beneficial, it is a priority to define robust molecular subtypes using clustering methods applied to high-dimensional biological data. If each of these methods produces different numbers of clusters for the same data, it is difficult to achieve an optimal solution. Here, we introduce “polyClustR”, a tool that reconciles clusters identified by different methods into subtype “communities” using a hypergeometric test or a measure of relative proportion of common samples. RESULTS: The polyClustR pipeline was initially tested using a breast cancer dataset to demonstrate how results are compatible with and add to the understanding of this well-characterised cancer. Two uveal melanoma datasets were then utilised to identify and validate novel subtype communities with significant metastasis-free prognostic differences and associations with known chromosomal aberrations. CONCLUSION: We demonstrate the value of the polyClustR approach of applying multiple consensus clustering algorithms and systematically reconciling the results in identifying novel subtype communities of two cancer types, which nevertheless are compatible with established understanding of these diseases. An R implementation of the pipeline is available at: https://github.com/syspremed/polyClustR ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2204-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-25 /pmc/articles/PMC5970540/ /pubmed/29801433 http://dx.doi.org/10.1186/s12859-018-2204-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Methodology Article
Eason, Katherine
Nyamundanda, Gift
Sadanandam, Anguraj
polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance
title polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance
title_full polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance
title_fullStr polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance
title_full_unstemmed polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance
title_short polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance
title_sort polyclustr: defining communities of reconciled cancer subtypes with biological and prognostic significance
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970540/
https://www.ncbi.nlm.nih.gov/pubmed/29801433
http://dx.doi.org/10.1186/s12859-018-2204-4
work_keys_str_mv AT easonkatherine polyclustrdefiningcommunitiesofreconciledcancersubtypeswithbiologicalandprognosticsignificance
AT nyamundandagift polyclustrdefiningcommunitiesofreconciledcancersubtypeswithbiologicalandprognosticsignificance
AT sadanandamanguraj polyclustrdefiningcommunitiesofreconciledcancersubtypeswithbiologicalandprognosticsignificance