Mutual-assistance learning for trustworthy biomarker discovery and disease prediction.

Integrating and analyzing multiple omics datasets, such as genomics, environmental influences, and imaging endophenotypes, has yielded an abundance of candidate biomarkers. However, translating such findings into beneficial clinical knowledge for disease prediction remains challenging. This becomes even more challenging when studying interpretable high-order feature interactions such as gene-environment interaction (G$\times $E) to understand the etiology. To fill this gap, we draw on the idea of mutual-assistance (MA) learning and accordingly propose a fresh and powerful scheme, referred to as mutual-assistance causal biomarker discovery and stable disease prediction approach (MA-CBxDP). Specifically, we design an interpretable bi-directional mapping framework, integrated with a causal feature interaction module, to extract co-expression patterns across different modalities and identify trustworthy biomarkers including G$\times $E. A cooperative prediction module is further incorporated to ensure accurate diagnosis and identification of causal effects for pathogenesis. Importantly, biomarker discovery and disease prediction can mutually reinforce each other, helping to provide novel insights into chronic diseases. Furthermore, in light of the large computational burden incurred by the high-dimensional interactions, we devise a rapid strategy and extend it to a more practical but challenging chromosome-wide setting. We conduct extensive experiments on two databases under three tasks, i.e. multimodal correlation, disease diagnosis, and trait prediction. MA-CBxDP establishes new state-of-the-art results in predicting clinical scores and disease status classification, while maintaining exceptional interpretability, verifying its flexibility and versatility in practical applications.