Application of orthogonal sparse joint non-negative matrix factorization based on connectivity in Alzheimer's disease research.

Based on the mining of micro- and macro-relationships of genetic variation and brain imaging data, imaging genetics has been widely applied in the early diagnosis of Alzheimer's disease (AD). However, effective integration of prior knowledge remains a barrier to determining the biological mechanism of AD. This paper proposes a new connectivity-based orthogonal sparse joint non-negative matrix factorization (OSJNMF-C) method based on integrating the structural magnetic resonance image, single nucleotide polymorphism and gene expression data of AD patients; the correlation information, sparseness, orthogonal constraint and brain connectivity information between the brain image data and genetic data are designed as constraints in the proposed algorithm, which efficiently improved the accuracy and convergence through multiple iterative experiments. Compared with the competitive algorithm, OSJNMF-C has significantly smaller related errors and objective function values than the competitive algorithm, showing its good anti-noise performance. From the biological point of view, we have identified some biomarkers and statistically significant relationship pairs of AD/mild cognitive impairment (MCI), such as rs75277622 and BCL7A, which may affect the function and structure of multiple brain regions. These findings will promote the prediction of AD/MCI.