A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functions

<p>Abstract</p> <p>Background</p> <p>In genomic medical studies, one of the major objectives is to identify genomic factors with a prognostic impact on time-to-event outcomes so as to provide new insights into the disease process. Selection usually relies on statistical...

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Main Authors: Moreau Thierry, Rouam Sigrid, Broët Philippe
Format: Article
Language:English
Published: BMC 2011-03-01
Series:BMC Medical Research Methodology
Online Access:http://www.biomedcentral.com/1471-2288/11/28
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author Moreau Thierry
Rouam Sigrid
Broët Philippe
author_facet Moreau Thierry
Rouam Sigrid
Broët Philippe
author_sort Moreau Thierry
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>In genomic medical studies, one of the major objectives is to identify genomic factors with a prognostic impact on time-to-event outcomes so as to provide new insights into the disease process. Selection usually relies on statistical univariate indices based on the Cox model. Such model assumes proportional hazards (PH) which is unlikely to hold for each genomic marker.</p> <p>Methods</p> <p>In this paper, we introduce a novel pseudo-R<sup>2 </sup>measure derived from a crossing hazards model and designed for the selection of markers with crossing effects. The proposed index is related to the score statistic and quantifies the extent of a genomic factor to separate patients according to their survival times and marker measurements. We also show the importance of considering genomic markers with crossing effects as they potentially reflect the complex interplay between markers belonging to the same pathway.</p> <p>Results</p> <p>Simulations show that our index is not affected by the censoring and the sample size of the study. It also performs better than classical indices under the crossing hazards assumption. The practical use of our index is illustrated in a lung cancer study. The use of the proposed pseudo-R<sup>2 </sup>allows the identification of cell-cycle dependent genes not identified when relying on the PH assumption.</p> <p>Conclusions</p> <p>The proposed index is a novel and promising tool for selecting markers with crossing hazards effects.</p>
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spelling doaj.art-8474ece56eb7411fbe84ef79b88f4a102022-12-21T20:40:53ZengBMCBMC Medical Research Methodology1471-22882011-03-011112810.1186/1471-2288-11-28A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functionsMoreau ThierryRouam SigridBroët Philippe<p>Abstract</p> <p>Background</p> <p>In genomic medical studies, one of the major objectives is to identify genomic factors with a prognostic impact on time-to-event outcomes so as to provide new insights into the disease process. Selection usually relies on statistical univariate indices based on the Cox model. Such model assumes proportional hazards (PH) which is unlikely to hold for each genomic marker.</p> <p>Methods</p> <p>In this paper, we introduce a novel pseudo-R<sup>2 </sup>measure derived from a crossing hazards model and designed for the selection of markers with crossing effects. The proposed index is related to the score statistic and quantifies the extent of a genomic factor to separate patients according to their survival times and marker measurements. We also show the importance of considering genomic markers with crossing effects as they potentially reflect the complex interplay between markers belonging to the same pathway.</p> <p>Results</p> <p>Simulations show that our index is not affected by the censoring and the sample size of the study. It also performs better than classical indices under the crossing hazards assumption. The practical use of our index is illustrated in a lung cancer study. The use of the proposed pseudo-R<sup>2 </sup>allows the identification of cell-cycle dependent genes not identified when relying on the PH assumption.</p> <p>Conclusions</p> <p>The proposed index is a novel and promising tool for selecting markers with crossing hazards effects.</p>http://www.biomedcentral.com/1471-2288/11/28
spellingShingle Moreau Thierry
Rouam Sigrid
Broët Philippe
A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functions
BMC Medical Research Methodology
title A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functions
title_full A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functions
title_fullStr A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functions
title_full_unstemmed A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functions
title_short A pseudo-R<sup>2 </sup>measure for selecting genomic markers with crossing hazards functions
title_sort pseudo r sup 2 sup measure for selecting genomic markers with crossing hazards functions
url http://www.biomedcentral.com/1471-2288/11/28
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