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Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression

BACKGROUND: Important objectives in cancer research are the prediction of a patient’s risk based on molecular measurements such as gene expression data and the identification of new prognostic biomarkers (e.g. genes). In clinical practice, this is often challenging because patient cohorts are typica...

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Autores principales: Madjar, Katrin, Zucknick, Manuela, Ickstadt, Katja, Rahnenführer, Jörg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665528/
https://www.ncbi.nlm.nih.gov/pubmed/34895139
http://dx.doi.org/10.1186/s12859-021-04483-z
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author Madjar, Katrin
Zucknick, Manuela
Ickstadt, Katja
Rahnenführer, Jörg
author_facet Madjar, Katrin
Zucknick, Manuela
Ickstadt, Katja
Rahnenführer, Jörg
author_sort Madjar, Katrin
collection PubMed
description BACKGROUND: Important objectives in cancer research are the prediction of a patient’s risk based on molecular measurements such as gene expression data and the identification of new prognostic biomarkers (e.g. genes). In clinical practice, this is often challenging because patient cohorts are typically small and can be heterogeneous. In classical subgroup analysis, a separate prediction model is fitted using only the data of one specific cohort. However, this can lead to a loss of power when the sample size is small. Simple pooling of all cohorts, on the other hand, can lead to biased results, especially when the cohorts are heterogeneous. RESULTS: We propose a new Bayesian approach suitable for continuous molecular measurements and survival outcome that identifies the important predictors and provides a separate risk prediction model for each cohort. It allows sharing information between cohorts to increase power by assuming a graph linking predictors within and across different cohorts. The graph helps to identify pathways of functionally related genes and genes that are simultaneously prognostic in different cohorts. CONCLUSIONS: Results demonstrate that our proposed approach is superior to the standard approaches in terms of prediction performance and increased power in variable selection when the sample size is small. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04483-z.
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spelling pubmed-86655282021-12-13 Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression Madjar, Katrin Zucknick, Manuela Ickstadt, Katja Rahnenführer, Jörg BMC Bioinformatics Methodology Article BACKGROUND: Important objectives in cancer research are the prediction of a patient’s risk based on molecular measurements such as gene expression data and the identification of new prognostic biomarkers (e.g. genes). In clinical practice, this is often challenging because patient cohorts are typically small and can be heterogeneous. In classical subgroup analysis, a separate prediction model is fitted using only the data of one specific cohort. However, this can lead to a loss of power when the sample size is small. Simple pooling of all cohorts, on the other hand, can lead to biased results, especially when the cohorts are heterogeneous. RESULTS: We propose a new Bayesian approach suitable for continuous molecular measurements and survival outcome that identifies the important predictors and provides a separate risk prediction model for each cohort. It allows sharing information between cohorts to increase power by assuming a graph linking predictors within and across different cohorts. The graph helps to identify pathways of functionally related genes and genes that are simultaneously prognostic in different cohorts. CONCLUSIONS: Results demonstrate that our proposed approach is superior to the standard approaches in terms of prediction performance and increased power in variable selection when the sample size is small. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04483-z. BioMed Central 2021-12-11 /pmc/articles/PMC8665528/ /pubmed/34895139 http://dx.doi.org/10.1186/s12859-021-04483-z Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Methodology Article
Madjar, Katrin
Zucknick, Manuela
Ickstadt, Katja
Rahnenführer, Jörg
Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression
title Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression
title_full Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression
title_fullStr Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression
title_full_unstemmed Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression
title_short Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression
title_sort combining heterogeneous subgroups with graph-structured variable selection priors for cox regression
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665528/
https://www.ncbi.nlm.nih.gov/pubmed/34895139
http://dx.doi.org/10.1186/s12859-021-04483-z
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