Correlation-adjusted regression survival scores for high-dimensional variable selection
File(s)Welchowski_et_al-2019-Statistics_in_Medicine.pdf (1.01 MB)
Published version
Author(s)
Welchowski, Thomas
Zuber, Verena
Schmid, Matthias
Type
Journal Article
Abstract
Background: The development of classification methods for personalized medicine is highly dependent on the identification of predictive genetic markers. In survival analysis, it is often necessary to discriminate between influential and noninfluential markers. It is common to perform univariate screening using Cox scores, which quantify the associations between survival and each of the markers to provide a ranking. Since Cox scores do not account for dependencies between the markers, their use is suboptimal in the presence of highly correlated markers.
Methods: As an alternative to the Cox score, we propose the correlation‐adjusted regression survival (CARS) score for right‐censored survival outcomes. By removing the correlations between the markers, the CARS score quantifies the associations between the outcome and the set of “decorrelated” marker values. Estimation of the scores is based on inverse probability weighting, which is applied to log‐transformed event times. For high‐dimensional data, estimation is based on shrinkage techniques.
Results: The consistency of the CARS score is proven under mild regularity conditions. In simulations with high correlations, survival models based on CARS score rankings achieved higher areas under the precision‐recall curve than competing methods. Two example applications on prostate and breast cancer confirmed these results. CARS scores are implemented in the R package carSurv.
Conclusions: In research applications involving high‐dimensional genetic data, the use of CARS scores for marker selection is a favorable alternative to Cox scores even when correlations between covariates are low. Having a straightforward interpretation and low computational requirements, CARS scores are an easy‐to‐use screening tool in personalized medicine research.
Methods: As an alternative to the Cox score, we propose the correlation‐adjusted regression survival (CARS) score for right‐censored survival outcomes. By removing the correlations between the markers, the CARS score quantifies the associations between the outcome and the set of “decorrelated” marker values. Estimation of the scores is based on inverse probability weighting, which is applied to log‐transformed event times. For high‐dimensional data, estimation is based on shrinkage techniques.
Results: The consistency of the CARS score is proven under mild regularity conditions. In simulations with high correlations, survival models based on CARS score rankings achieved higher areas under the precision‐recall curve than competing methods. Two example applications on prostate and breast cancer confirmed these results. CARS scores are implemented in the R package carSurv.
Conclusions: In research applications involving high‐dimensional genetic data, the use of CARS scores for marker selection is a favorable alternative to Cox scores even when correlations between covariates are low. Having a straightforward interpretation and low computational requirements, CARS scores are an easy‐to‐use screening tool in personalized medicine research.
Date Issued
2019-06-15
Date Acceptance
2019-01-17
Citation
Statistics in Medicine, 2019, 38 (13), pp.2413-2427
ISSN
0277-6715
Publisher
Wiley
Start Page
2413
End Page
2427
Journal / Book Title
Statistics in Medicine
Volume
38
Issue
13
Copyright Statement
© 2019 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000466578800008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Mathematical & Computational Biology
Public, Environmental & Occupational Health
Medical Informatics
Medicine, Research & Experimental
Statistics & Probability
Research & Experimental Medicine
Mathematics
biomarker discovery
breast cancer
multigene signature
personalized medicine
prostate cancer
survival modeling
GENE-EXPRESSION
REGULARIZATION
GLYCINE
CANCER
Publication Status
Published
Date Publish Online
2019-02-22