GIRUS-net: A Multimodal Deep Learning Model Identifying Imaging and Genetic Biomarkers Linked to Alzheimer’s Disease Severity

We introduce an explainable deep neural architecture that combines brain structure with genetic influence to improve disease severity prediction in Alzheimer’s disease. Our framework consists of an encoder, a decoder, and a rank-consistent ordinal regression module. The encoder projects neural imaging and genetics data into a low-dimensional latent space regularized by the decoder. The ordinal regression module guides the feature embedding process to find discriminative patterns representative of disease severity. We also add a learnable dropout layer that learns feature importance and extracts explainable biomarkers from the data. We evaluate our model using structural MRI (sMRI) and Single Nucleotide Polymorphism (SNP) data provided by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. In 2-class severity classification comparison, our model has a median F-score of 0.86 (baseline median F-score range: 0.57-0.81). In 3-class classification comparison, our model’s median F-score is 0.50 (baseline range: 0.17 - 0.41). In 4-class classification comparison, our model’s median F-score is 0.40 (baseline range: 0.14 - 0.39). We demonstrate that our model provides improved disease diagnosis alongside sparse and clinically relevant biomarkers.Clinical relevance—This study provides a deep-learning model that can predict Alzheimer’s disease severity levels while identifying consistent and clinically relevant biomarkers.