GenDMR: A dynamic multimodal role-swapping network for identifying risk gene phenotypes

Recent studies have shown that integrating multimodal data fusion techniques for imaging and genetic features is beneficial for the etiological analysis and predictive diagnosis of Alzheimer's disease (AD). However, there are several critical flaws in current deep learning methods. Firstly, there has been insufficient discussion and exploration regarding the selection and encoding of genetic information. Secondly, due to the significantly superior classification value of AD imaging features compared to genetic features, many studies in multimodal fusion emphasize the strengths of imaging features, actively mitigating the influence of weaker features, thereby diminishing the learning of the unique value of genetic features. To address this issue, this study proposes the dynamic multimodal role-swapping network (GenDMR). In GenDMR, we develop a novel approach to encode the spatial organization of single nucleotide polymorphisms (SNPs), enhancing the representation of their genomic context. Additionally, to adaptively quantify the disease risk of SNPs and brain region, we propose a multi-instance attention module to enhance model interpretability. Furthermore, we introduce a dominant modality selection module and a contrastive self-distillation module, combining them to achieve a dynamic teacher-student role exchange mechanism based on dominant and auxiliary modalities for bidirectional co-updating of different modal data. Finally, GenDMR achieves state-of-the-art performance on the ADNI public dataset and visualizes attention to different SNPs, focusing on confirming 12 potential high-risk genes related to AD, including the most classic APOE and recently highlighted significant risk genes. This demonstrates GenDMR's interpretable analytical capability in exploring AD genetic features, providing new insights and perspectives for the development of multimodal data fusion techniques.