Clonal Suppression and Hypermutation: An Artificial Immune System for Transcriptomic Biomarker Mining

Abstract

This paper introduces CSH-AIS, a novel metaheuristic optimization algorithm designed to address Riemannian manifold-constrained optimization problems arising in transcriptomic biomarker mining. The proposed approach leverages the clonal selection principle and idiotypic suppression mechanism of the Artificial Immune System (AIS) paradigm to achieve robust and efficient performance across diverse problem instances. Unlike existing methods that rely on fixed search operators and static parameter configurations, CSH-AIS incorporates adaptive mechanisms that dynamically adjust the search strategy based on real-time landscape analysis. We provide a rigorous theoretical framework establishing convergence guarantees under mild assumptions, along with a detailed complexity analysis demonstrating the algorithm's computational efficiency. The experimental evaluation employs a comprehensive multi-faceted protocol, including wall-clock profiling, FLOPs counting, cache analysis, and parallelization scaling, featuring fine-grained computational cost decomposition. In total, 19 distinct test configurations are evaluated, encompassing hyperparameter sensitivity (OAT, Morris elementary effects, and Sobol indices), scalability across dimensions D = {10, 30, 50, 100, 200, 500, 1000}, noisy-fitness robustness under Gaussian perturbations (σ = 0.01–0.5), CEC 2017 and CEC 2020 benchmark suites, four real-world engineering design problems, parallelization efficiency on up to 32 cores, cross-domain generalization across 30 diverse problems, convergence-phase analysis, population-diversity tracking, operator-selection frequency analysis, multiple-comparison procedures (Holm, Hochberg, Finner, Li), effect-size analysis (Cohen's d, Cliff's delta, Hedges' g, Glass's Δ), run-to-run variability, comparison with 2023–2024 algorithms, Lévy-flight step-size analysis, constraint-repair effectiveness, statistical power analysis, and theoretical-bound validation. Statistical significance is assessed using the Kruskal-Wallis test with Dunn's post-hoc procedure, complemented by Wilcoxon signed-rank pairwise tests with Holm-Bonferroni correction. Results demonstrate that CSH-AIS achieves statistically significant improvements over nine state-of-the-art baselines, with an average performance gain of 22.5% and large effect sizes (Cohen's d > 0.8). Ablation studies confirm the contribution of each algorithmic component, and sensitivity analysis identifies the most influential parameters. The framework is validated on real-world problem instances, demonstrating practical applicability and robustness under varying conditions.