TILDA-X: Transcriptome-Informed Lung Cancer Disparities via Explainable AI

作者：Masrur Sobhan, M. Islam, Mary Jo Trepka, Gregory E. Holt, Charles J. Dimitroff, Ananda Mohan Mondal · 发表于：Cancers · 年份：2025 · DOI：10.3390/cancers17213454 · 被引用次数：2 · 研究领域：Lung Cancer Treatments and Mutations、Ferroptosis and cancer prognosis、Lung Cancer Diagnosis and Treatment

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality, with disparities in incidence and outcomes observed across different racial and sex groups. Identifying both patient-specific and cohort-specific disparity biomarkers is critical for developing targeted treatments. The lung cancer dataset is highly imbalanced across races, leading to biased results in disparity information if classification is based on race. METHOD: This study developed an explainable artificial intelligence-based framework, TILDA-X, which designs classification models based on disease conditions instead of races to mitigate racial imbalance in the dataset and applies explainable AI to delineate patient-specific disparity information. A lung cancer transcriptome dataset with three disease conditions-lung adenocarcinoma, lung squamous cell carcinoma, and healthy samples-was used to develop classification models. Applying a bottom-up approach from patient-specific disparity information, the cohort-specific disparity information is discovered for different racial and sex groups, African American males, European American males, African American females, and European American females. RESULTS: Classification based on disease conditions achieved accuracy between 88% and 100% for minority groups (African American males and females), whereas it was only between 0% and 16% for race-based classification, which underscores the significance of the proposed approach. Functional analysis of sub-cohort-...