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Main Authors: Sun, Ao, Deng, Zhanwang, Zhao, Jiahui, Li, Hang, Zhou, Xiao-Hua
Format: Preprint
Published: 2025
Subjects:
Online Access:https://arxiv.org/abs/2509.02090
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author Sun, Ao
Deng, Zhanwang
Zhao, Jiahui
Li, Hang
Zhou, Xiao-Hua
author_facet Sun, Ao
Deng, Zhanwang
Zhao, Jiahui
Li, Hang
Zhou, Xiao-Hua
contents In clinical practice, multiple biomarkers are used for disease diagnosis, but their individual accuracies are often suboptimal, with only a few proving directly relevant. Effectively selecting and combining biomarkers can significantly improve diagnostic accuracy. Existing methods often optimize metrics like the Area Under the ROC Curve (AUC) or the Youden index. However, optimizing AUC does not yield estimates for optimal cutoff values, and the Youden index assumes equal weighting of sensitivity and specificity, which may not reflect clinical priorities where these metrics are weighted differently. This highlights the need for methods that can flexibly accommodate such requirements. In this paper, we present a novel framework for selecting and combining biomarkers to maximize a weighted version of the Youden index. We introduce a smoothed estimator based on the weighted Youden index and propose a penalized version using the SCAD penalty to enhance variable selection. To handle the non-convexity of the objective function and the non-smoothness of the penalty, we develop an efficient algorithm, also applicable to other non-convex optimization problems. Simulation studies demonstrate the performance and efficiency of our method, and we apply it to construct a diagnostic scale for dermatitis.
format Preprint
id arxiv_https___arxiv_org_abs_2509_02090
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Biomarkers selection and combination based on the weighted Youden index
Sun, Ao
Deng, Zhanwang
Zhao, Jiahui
Li, Hang
Zhou, Xiao-Hua
Methodology
In clinical practice, multiple biomarkers are used for disease diagnosis, but their individual accuracies are often suboptimal, with only a few proving directly relevant. Effectively selecting and combining biomarkers can significantly improve diagnostic accuracy. Existing methods often optimize metrics like the Area Under the ROC Curve (AUC) or the Youden index. However, optimizing AUC does not yield estimates for optimal cutoff values, and the Youden index assumes equal weighting of sensitivity and specificity, which may not reflect clinical priorities where these metrics are weighted differently. This highlights the need for methods that can flexibly accommodate such requirements. In this paper, we present a novel framework for selecting and combining biomarkers to maximize a weighted version of the Youden index. We introduce a smoothed estimator based on the weighted Youden index and propose a penalized version using the SCAD penalty to enhance variable selection. To handle the non-convexity of the objective function and the non-smoothness of the penalty, we develop an efficient algorithm, also applicable to other non-convex optimization problems. Simulation studies demonstrate the performance and efficiency of our method, and we apply it to construct a diagnostic scale for dermatitis.
title Biomarkers selection and combination based on the weighted Youden index
topic Methodology
url https://arxiv.org/abs/2509.02090