How important are the genes to explain the outcome - the asymmetric Shapley value as an honest importance metric for high-dimensional features

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Main Authors: van de Wiel, Mark A., Goedhart, Jeroen, Jullum, Martin, Aas, Kjersti
Format: Preprint
Published: 2026
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author van de Wiel, Mark A.
Goedhart, Jeroen
Jullum, Martin
Aas, Kjersti
author_facet van de Wiel, Mark A.
Goedhart, Jeroen
Jullum, Martin
Aas, Kjersti
contents In clinical prediction settings the importance of a high-dimensional feature like genomics is often assessed by evaluating the change in predictive performance when adding it to a set of traditional clinical variables. This approach is questionable, because it does not account for collinearity nor known directionality of dependencies between variables. We suggest to use asymmetric Shapley values as a more suitable alternative to quantify feature importance in the context of a mixed-dimensional prediction model. We focus on a setting that is particularly relevant in clinical prediction: disease state as a mediating variable for genomic effects, with additional confounders for which the direction of effects may be unknown. We derive efficient algorithms to compute local and global asymmetric Shapley values for this setting. The former are shown to be very useful for inference, whereas the latter provide interpretation by decomposing any predictive performance metric into contributions of the features. Throughout, we illustrate our framework by a leading example: the prediction of progression-free survival for colorectal cancer patients.
format Preprint
id arxiv_https___arxiv_org_abs_2603_05317
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle How important are the genes to explain the outcome - the asymmetric Shapley value as an honest importance metric for high-dimensional features
van de Wiel, Mark A.
Goedhart, Jeroen
Jullum, Martin
Aas, Kjersti
Machine Learning
In clinical prediction settings the importance of a high-dimensional feature like genomics is often assessed by evaluating the change in predictive performance when adding it to a set of traditional clinical variables. This approach is questionable, because it does not account for collinearity nor known directionality of dependencies between variables. We suggest to use asymmetric Shapley values as a more suitable alternative to quantify feature importance in the context of a mixed-dimensional prediction model. We focus on a setting that is particularly relevant in clinical prediction: disease state as a mediating variable for genomic effects, with additional confounders for which the direction of effects may be unknown. We derive efficient algorithms to compute local and global asymmetric Shapley values for this setting. The former are shown to be very useful for inference, whereas the latter provide interpretation by decomposing any predictive performance metric into contributions of the features. Throughout, we illustrate our framework by a leading example: the prediction of progression-free survival for colorectal cancer patients.
title How important are the genes to explain the outcome - the asymmetric Shapley value as an honest importance metric for high-dimensional features
topic Machine Learning
url https://arxiv.org/abs/2603.05317