Fairness-aware Supervised Hierarchical Contrastive Semantic Learning for Sexual Dimorphism Analysis

MotivationSexual dimorphism is a fundamental biological determinant driving systematic differences in disease susceptibility, progression, and clinical outcomes. However, current AI-based genomic models often exhibit algorithmic bias and fail to capture these sex-specific mechanisms, creating a critical barrier to unbiased precision medicine. Ensuring fairness in the context of sexual dimorphism requires understanding and addressing the distinct biological mechanisms functioning in each sex, rather than focusing solely on equalizing predictive performance. ResultsWe propose a fairness-aware supervised hierarchical contrastive learning approach, called FairHICON, to discover unbiased sex-common and sex-specific genomic drivers. Evaluations on cancer and asthma transcriptomic datasets demonstrate that FairHICON significantly outperforms state-of-the-art benchmarks, improving predictive performance by up to 9% while effectively reducing the performance gap between male and female cohorts. Furthermore, prognostic validation confirms that the identified sex-specific pathways stratify patient survival significantly better within their corresponding sex groups. This validates FairHICON to elucidate the molecular heterogeneity of sexual dimorphism, advancing inclusive precision medicine. Availability and implementationThe source code and data is available at https://github.com/datax-lab/FairHICON.