Identify Biomarkers of Alzheimer's Disease Based on Multi-task Canonical Correlation Analysis and Regression Model.

Imaging genetics using imaging technology is regarded as a neuroanatomical phenotype to evaluate gene single nucleotide polymorphisms and their effects on the structure and function of different brain regions. It plays a vital role in bridging the initial understanding of the genetic basis of brain structure and dysfunction. Sparse canonical correlation analysis (SCCA) has become a widespread technique in this field because of its powerful ability to identify bivariate relationships and feature selection. Since most traditional SCCA algorithms assume that the input features are independent, this method obviously cannot be used to analyze genetic image data. The MT-SCCA model is unsupervised and cannot identify the genotype-phenotype associations for diagnostic guidance. Meanwhile, a single biological clinical index cannot fully reflect the physiological process of a comprehensive disease. Therefore, it is necessary to find biomarkers that can reflect Alzheimer's disease and physiological functions that can more comprehensively reflect the development of the disease. This article uses a multi-task sparse canonical correlation analysis and regression (MT-SCCAR) model to combine the annual depression level total score (GDSCALE), clinical dementia assessment scale (GLOBAL CDR), functional activity questionnaire (FAQ), and neuropsychiatric Symptom Questionnaire (NPI-Q) in this paper. These four clinical data are used as compensation information and embedded in the algorithm in a linear regression manner. It also reflects its superiority and robustness compared to traditional correlation analysis methods on actual and simulated data. Meanwhile, compared with MT-SCCA, the model utilized in this paper obtains a higher gene-ROI weight and identifies clearer biomarkers, which provides a practical basis for the study of complex human disease pathology.

Identifying Imaging Genetics Biomarkers of Alzheimer's Disease by Multi-Task Sparse Canonical Correlation Analysis and Regression.

Imaging genetics combines neuroimaging and genetics to assess the relationships between genetic variants and changes in brain structure and metabolism. Sparse canonical correlation analysis (SCCA) models are well-known tools for identifying meaningful biomarkers in imaging genetics. However, most SCCA models incorporate only diagnostic status information, which poses challenges for finding disease-specific biomarkers. In this study, we proposed a multi-task sparse canonical correlation analysis and regression (MT-SCCAR) model to reveal disease-specific associations between single nucleotide polymorphisms and quantitative traits derived from multi-modal neuroimaging data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. MT-SCCAR uses complementary information carried by multiple-perspective cognitive scores and encourages group sparsity on genetic variants. In contrast with two other multi-modal SCCA models, MT-SCCAR embedded more accurate neuropsychological assessment information through linear regression and enhanced the correlation coefficients, leading to increased identification of high-risk brain regions. Furthermore, MT-SCCAR identified primary genetic risk factors for Alzheimer's disease (AD), including rs429358, and found some association patterns between genetic variants and brain regions. Thus, MT-SCCAR contributes to deciphering genetic risk factors of brain structural and metabolic changes by identifying potential risk biomarkers.