Abstract
sAlzheimer’s disease (AD) is a neurodegenerative disorder and is represented by complicated biological mechanisms and complexity of brain tissue. Our understanding of the complicated molecular architecture that contributes to AD progression benefits from performing comprehensive and systemic investigations with multi-layered molecular and biological data from different brain regions. Since recently different independent studies generated various omics data in different brain regions of AD patients, multi-omics data integration can be a useful resource for better comprehensive understanding of AD. Here we present a web platform, ADAS-viewer, that provides researchers with the ability to comprehensively investigate and visualize multi-omics data from multiple brain regions of AD patients. ADAS-viewer offers means to identify functional changes in transcript and exon expression (i.e., alternative splicing) along with associated genetic or epigenetic regulatory effects. Specifically, it integrates genomic, transcriptomic, methylation, and miRNA data collected from seven different brain regions (cerebellum, temporal cortex, dorsolateral prefrontal cortex, frontal pole, inferior frontal gyrus, parahippocampal gyrus, and superior temporal gyrus) across three independent cohort datasets. ADAS-viewer is particularly useful as a web-based application for analyzing and visualizing multi-omics data across multiple brain regions at both transcript and exon level, allowing the identification of candidate biomarkers of Alzheimer’s disease.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder rooted in complicated biological mechanisms and the inherent complexity of brain tissue1,2
We present ADAS-viewer as having potential utility for identifying biomarkers and developing further understanding of AD pathology with respect to differential alternative splicing and the genetic/epigenetic regulation of gene expression across seven brain regions
ADAS-viewer is currently available at http://genomics.chpc.utah. edu/AD, and a tutorial is available at http://genomics.chpc.utah. edu/AD/manual/Manual.pdf
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder rooted in complicated biological mechanisms and the inherent complexity of brain tissue. Each area of the human brain has a unique function; for example, the parietal cortex is uniquely involved in the movement and incorporation of signals from other cortices. Each area of the human brain has a unique function; for example, the parietal cortex is uniquely involved in the movement and incorporation of signals from other cortices3,4 This tissue-level complexity is reflected in transcriptomic and proteomic profiles of the brain, which feature dynamic and regionspecific patterns across functionally different brain regions, including in the context of AD5,6. Many alternatively spliced genes have been identified in AD cases; in addition, GWAS studies have identified a large set of genetic variants associated with the onset and progression of AD4,11,12 Integration of these findings into multi-omics analyses is essential for the functional annotation of identified genetic variants
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