Development of a Shapley Additive Explanations (SHAP)-Interpretable Model for Cardiovascular Risk Stratification in Type 2 Diabetes Mellitus: Implications of MDA-Modified Protein Adducts and Autoantibodies.

Chien-Yi Hsu, Shou-Cheng Lu, Liang-Wei Lin, Chu-Heng Yen, Hung-Tse Lin, Shao-Chun Lin, Ching-Yu Lin, Chao-Lien Liu

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Article in ACS omega, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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8 authors.

Chien-Yi HsuDivision of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine,Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan.

Shou-Cheng LuDepartment of Laboratory Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.

Liang-Wei LinDepartment of Laboratory Medicine, Taiwan Adventist Hospital, Taipei 10556, Taiwan.

Chu-Heng YenDepartment of Laboratory Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.

Hung-Tse LinDepartment of Laboratory Medicine, LinKou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.

Shao-Chun LinDepartment of Pharmacy, Chia Nan University of Pharmacy & Science, Tainan City 717301, Taiwan.

Ching-Yu LinSchool of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Chao-Lien LiuSchool of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Coronary artery disease (CAD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM). This study explores the two-hit oxidative-immune hypothesis by evaluating malondialdehyde (MDA)-modified protein (MDA-protein) adducts and their corresponding autoantibodies for precise and fair CAD severity stratification and classification. Novel MDA-peptide epitopes (apolipoprotein B-100 (ApoB-100), fibronectin (FINC), and complement C4A/C4B (C4A/C4B)) were identified via proteomics, and plasma levels of MDA, adducts, and autoantibodies were measured in 165 Taiwanese T2DM patients. Multivariate logistic regression estimated odds ratios (ORs) per 1-SD increase. Machine learning with Shapley additive explanations (SHAP)-interpretable analysis and nested cross validation distinguished obstructive from nonobstructive CAD. Fairness was assessed across age and sex subgroups. MDA (OR 3.148) and MDA-protein adducts (OR 2.090) were independent markers associated with advanced CAD severity, while IgG anti-ApoB-100

Identifiers

PMID42662675

DOI10.1021/acsomega.6c05628

PMCPMC13520431

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.