Identification of image genetic biomarkers of Alzheimer's disease by orthogonal structured sparse canonical correlation analysis based on a diagnostic information fusion.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease, and its incidence increases yearly. Because AD patients will have cognitive impairment and personality changes, it has caused a heavy burden on the family and society. Image genetics takes the structure and function of the brain as a phenotype and studies the influence of genetic variation on the structure and function of the brain. Based on the structural magnetic resonance imaging data and transcriptome data of AD and healthy control samples in the Alzheimer's Disease Neuroimaging Disease database, this paper proposed the use of an orthogonal structured sparse canonical correlation analysis for diagnostic information fusion algorithm. The algorithm added structural constraints to the region of interest (ROI) of the brain. Integrating the diagnostic information of samples can improve the correlation performance between samples. The results showed that the algorithm could extract the correlation between the two modal data and discovered the brain regions most affected by multiple risk genes and their biological significance. In addition, we also verified the diagnostic significance of risk ROIs and risk genes for AD. The code of the proposed algorithm is available at https://github.com/Wanguangyu111/OSSCCA-DIF.

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.

Detecting Biomarkers of Alzheimer's Disease Based on Multi-constrained Uncertainty-Aware Adaptive Sparse Multi-view Canonical Correlation Analysis.

Image genetics mainly explores the pathogenesis of Alzheimer's disease (AD) by studying the relationship between genetic data (such as SNP, gene expression data, and DNA methylation) and imaging data (such as structural MRI (sMRI), fMRI, and PET). Most of the existing research on brain imaging genomics uses two-way or three-way bi-multivariate methods to explore the correlation analysis between genes and brain imaging. However, many of these methods are still affected by the gradient domination or cannot take into account the effect of feature redundancy on the results, so that the typical correlation coefficient and program running speed are not significantly improved. In order to solve the above problems, this paper proposes a multi-constrained uncertainty-aware adaptive sparse multi-view canonical correlation analysis method (MC-unAdaSMCCA) to explore associations among SNPs, gene expression data, and sMRI; that is, based on traditional unAdaSMCCA, orthogonal constraints are imposed on the weights of the three data features through linear programming, which can reduce the redundancy of feature weights to improve the correlation between the data and reduce the complexity of the algorithm to significantly speed up the running speed of the program. Three adaptive sparse multi-view canonical correlation analysis methods are used as benchmarks to evaluate the difference between real neuroimaging data and synthetic data. Compared with the other three methods, our proposed method has obtained better or comparable typical correlation coefficients and typical weights. Moreover, the following experimental results show that the MC-unAdaSMCCA method cannot only identify biomarkers related to AD and mild cognitive impairment (MCI), but also has a strong ability to resist noise and process high-dimensional data. Therefore, our proposed method provides a reliable approach to multi-modal imaging genetic researches.

Genome-wide variant-based study of genetic effects with the largest neuroanatomic coverage.

BACKGROUND: Brain image genetics provides enormous opportunities for examining the effects of genetic variations on the brain. Many studies have shown that the structure, function, and abnormality (e.g., those related to Alzheimer's disease) of the brain are heritable. However, which genetic variations contribute to these phenotypic changes is not completely clear. Advances in neuroimaging and genetics have led us to obtain detailed brain anatomy and genome-wide information. These data offer us new opportunities to identify genetic variations such as single nucleotide polymorphisms (SNPs) that affect brain structure. In this paper, we perform a genome-wide variant-based study, and aim to identify top SNPs or SNP sets which have genetic effects with the largest neuroanotomic coverage at both voxel and region-of-interest (ROI) levels. Based on the voxelwise genome-wide association study (GWAS) results, we used the exhaustive search to find the top SNPs or SNP sets that have the largest voxel-based or ROI-based neuroanatomic coverage. For SNP sets with >2 SNPs, we proposed an efficient genetic algorithm to identify top SNP sets that can cover all ROIs or a specific ROI. RESULTS: We identified an ensemble of top SNPs, SNP-pairs and SNP-sets, whose effects have the largest neuroanatomic coverage. Experimental results on real imaging genetics data show that the proposed genetic algorithm is superior to the exhaustive search in terms of computational time for identifying top SNP-sets. CONCLUSIONS: We proposed and applied an informatics strategy to identify top SNPs, SNP-pairs and SNP-sets that have genetic effects with the largest neuroanatomic coverage. The proposed genetic algorithm offers an efficient solution to accomplish the task, especially for identifying top SNP-sets.