Qumsiyeh, EmmaBakir-Gungor, BurcuYousef, Malik2025-10-202025-10-202025979833156656297983315665552165-0608https://doi.org/10.1109/SIU66497.2025.11112241Integrating biological prior knowledge for disease gene associations has shown significant promise in discovering new biomarkers with potential translational applications. This work investigates the application of a multi-algorithm machine learning framework based on the Grouping-Scoring-Modeling (G-S-M) approach for improving the prediction of complex diseases. The study identifies the primary gene and miRNA interactions in various complex diseases with the help of miRGediNET, which is a machine-learning based tool that integrates data from three biological databases. Traditional methods have only focused on independence between features; the G-S-M method focuses on aggregating genes based on biological interactions, pinpointing the scoring of gene groups for a disease, and modeling its predictive capability using advanced machine learning algorithms. In this research paper, seven algorithms, including Support Vector Machine, Decision Tree, and CatBoost, were applied to eight datasets extracted from the GEO database. This framework proved very robust in ranking gene clusters, thus predicting critical biomarkers while doing 100-fold randomized cross-validation within the evaluation. The results indicate this approach's high potential for refining disease and supporting research for choosing the best algorithm that can provide biological insights and computational advances.eninfo:eu-repo/semantics/closedAccessBiological Integrative ApproachMachine LearningFeature SelectionGrouping-Scoring-Modeling (G-S-M) ApproachRobust Rank AggregationBiomarkersConference Object10.1109/SIU66497.2025.111122412-s2.0-105015435814