An Improved Deep Semi-supervised JNMF Method for Biomarker Extraction of Alzheimer's Disease.

Imaging genetics is an approach that explores the underlying mechanisms of brain disorders such as Alzheimer's disease (AD) by analyzing the correlation between neuroimaging and genetic data. Traditional non-negative matrix factorization (NMF) algorithms are based on linear assumptions, which limits the potential of nonlinear feature extraction among multi-omics data. This study proposes a novel joint-connectivity-based deep semi-supervised non-negative matrix factorization (JCB-DSNMF) model to overcome this limitation and incorporate prior knowledge from both within and between different modalities of data. The model effectively integrates physiological constraints such as connectivity to identify regions of interest (ROI), risk genes, and risk SNP loci associated with AD patients. JCB-DSNMF outperformed other NMF-based algorithms, such as JDSNMF and NMF, in identifying and predicting biologically relevant biomarkers closely related to AD from essential modules. The accuracy of the selected features was further validated by constructing a diagnostic model with high classification accuracy, achieving an AUC value of 0.8621 on the test set. In particular, the brain region Putamen_L and the gene RALGAPB achieved AUC values of 0.903 and 0.924, respectively, highlighting the importance of these features in early AD diagnosis.