Fusion of Tree-induced Regressions for Clinico-genomic Data

Fuente: arXiv
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Bibliographic Details
Main Authors: Goedhart, Jeroen M., van de Wiel, Mark A., van Wieringen, Wessel N., Klausch, Thomas
Format: Preprint
Published: 2024
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author Goedhart, Jeroen M.
van de Wiel, Mark A.
van Wieringen, Wessel N.
Klausch, Thomas
author_facet Goedhart, Jeroen M.
van de Wiel, Mark A.
van Wieringen, Wessel N.
Klausch, Thomas
contents Cancer prognosis is often based on a set of omics covariates and a set of established clinical covariates such as age and tumor stage. Combining these two sets poses challenges. First, dimension difference: clinical covariates should be favored because they are low-dimensional and usually have stronger prognostic ability than high-dimensional omics covariates. Second, interactions: genetic profiles and their prognostic effects may vary across patient subpopulations. Last, redundancy: a (set of) gene(s) may encode similar prognostic information as a clinical covariate. To address these challenges, we combine regression trees, employing clinical covariates only, with a fusion-like penalized regression framework in the leaf nodes for the omics covariates. The fusion penalty controls the variability in genetic profiles across subpopulations. We prove that the shrinkage limit of the proposed method equals a benchmark model: a ridge regression with penalized omics covariates and unpenalized clinical covariates. Furthermore, the proposed method allows researchers to evaluate, for different subpopulations, whether the overall omics effect enhances prognosis compared to only employing clinical covariates. In an application to colorectal cancer prognosis based on established clinical covariates and 20,000+ gene expressions, we illustrate the features of our method.
format Preprint
id arxiv_https___arxiv_org_abs_2411_02396
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Fusion of Tree-induced Regressions for Clinico-genomic Data
Goedhart, Jeroen M.
van de Wiel, Mark A.
van Wieringen, Wessel N.
Klausch, Thomas
Methodology
Cancer prognosis is often based on a set of omics covariates and a set of established clinical covariates such as age and tumor stage. Combining these two sets poses challenges. First, dimension difference: clinical covariates should be favored because they are low-dimensional and usually have stronger prognostic ability than high-dimensional omics covariates. Second, interactions: genetic profiles and their prognostic effects may vary across patient subpopulations. Last, redundancy: a (set of) gene(s) may encode similar prognostic information as a clinical covariate. To address these challenges, we combine regression trees, employing clinical covariates only, with a fusion-like penalized regression framework in the leaf nodes for the omics covariates. The fusion penalty controls the variability in genetic profiles across subpopulations. We prove that the shrinkage limit of the proposed method equals a benchmark model: a ridge regression with penalized omics covariates and unpenalized clinical covariates. Furthermore, the proposed method allows researchers to evaluate, for different subpopulations, whether the overall omics effect enhances prognosis compared to only employing clinical covariates. In an application to colorectal cancer prognosis based on established clinical covariates and 20,000+ gene expressions, we illustrate the features of our method.
title Fusion of Tree-induced Regressions for Clinico-genomic Data
topic Methodology
url https://arxiv.org/abs/2411.02396