Background:
Recent development in neuroimaging and genetic testing technologies have made it possible to measure pathological features associated with Alzheimer's disease (AD) in vivo. Mining potential molecular markers of AD from high-dimensional, multi-modal neuroimaging and omics data will provide a new basis for early diagnosis and intervention in AD. In order to discover the real pathogenic mutation and even understand the pathogenic mechanism of AD, lots of machine learning methods have been designed and successfully applied to the analysis and processing of large-scale AD biomedical data.
Objective:
To introduce and summarize the applications and challenges of machine learning methods in Alzheimer's disease multi-source data analysis.
Methods:
The literature selected in the review is obtained from Google Scholar, PubMed, and Web of Science. The keywords of literature retrieval include Alzheimer's disease, bioinformatics, image genetics, genome-wide association research, molecular interaction network, multi-omics data integration, and so on.
Conclusion:
This study comprehensively introduces machine learning-based processing techniques for AD neuroimaging data and then shows the progress of computational analysis methods in omics data, such as the genome, proteome, and so on. Subsequently, machine learning methods for AD imaging analysis are also summarized. Finally, we elaborate on the current emerging technology of multi-modal neuroimaging, multi-omics data joint analysis, and present some outstanding issues and future research directions.
Introduction: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder in the elderly, which will eventually lead to dementia without an effective precaution and treatment. As a typical complex disease, the mechanism of AD's occurrence and development still lacks sufficient understanding. Research design and methods: In this study, we aim to directly analyze the relationship between DNA variants and phenotypes based on the whole genome sequencing data. Firstly, to enhance the biological meanings of our study, we annotate the deleterious variants and mapped them to nearest protein coding genes. Then, to eliminate the redundant features and reduce the burden of downstream analysis, a multi-objective evaluation strategy based on entropy theory is applied for ranking all candidate genes. Finally, we use multi-classifier XGBoost for classifying unbalanced data composed with 46 AD samples, 483 mild cognitive impairment (MCI) samples and 279 cognitive normal (CN) samples. Results: The experimental results on real whole genome sequencing data from Alzheimer's Disease Neuroimaging Initiative (ADNI) show that our method not only has satisfactory classification performance but also finds significance correlation between AD and RIN3, a known susceptibility gene of AD. In addition, pathway enrichment analysis was carried out using the top 20 feature genes, and three pathways were confirmed to be significantly related to the formation of AD. Conclusions: From the experimental results, we demonstrated that the efficacy of our proposed method has practical significance.
Motivation: At present, a number of correlation analysis methods between SNPs and ROIs have been devised to explore the pathogenic mechanism of Alzheimer's disease. However, some of the deficiencies inherent in these methods, including lack of statistical efficacy and biological meaning. This study aims at addressing issues: insufficient correlation by previous methods (relative high regression error) and the lack of biological meaning in association analysis. Results: In this paper, a novel three-stage SNPs and ROIs correlation analysis framework is proposed. Firstly, clustering algorithm is applied to remove the potential linkage unbalanced structure of two SNPs. Then, the group sparse model is used to introduce prior information such as gene structure and linkage unbalanced structure to select feature SNPs. After the above steps, each SNP has a weight vector corresponding to each ROI, and the importance of SNPs can be judged according to the weights in the feature vector, and then the feature SNPs can be selected. Finally, for the selected feature SNPS, a support vector machine regression model is used to implement the prediction of the ROIs phenotype values. The experimental results under multiple performance measures show that the proposed method has better accuracy than other methods.
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