Integrative-omics for discovery of network-level disease biomarkers: a case study in Alzheimer’s disease

作者：Linhui Xie, Bing He, Pradeep Varathan, Kwangsik Nho, Shannon L. Risacher, Andrew J. Saykin, Paul Salama, Jingwen Yan · 发表于：Briefings in Bioinformatics · 年份：2021 · DOI：10.1093/bib/bbab121 · 被引用次数：16 · 研究领域：Bioinformatics and Genomic Networks、Alzheimer's disease research and treatments、Genetic Associations and Epidemiology

A large number of genetic variations have been identified to be associated with Alzheimer's disease (AD) and related quantitative traits. However, majority of existing studies focused on single types of omics data, lacking the power of generating a community including multi-omic markers and their functional connections. Because of this, the immense value of multi-omics data on AD has attracted much attention. Leveraging genomic, transcriptomic and proteomic data, and their backbone network through functional relations, we proposed a modularity-constrained logistic regression model to mine the association between disease status and a group of functionally connected multi-omic features, i.e. single-nucleotide polymorphisms (SNPs), genes and proteins. This new model was applied to the real data collected from the frontal cortex tissue in the Religious Orders Study and Memory and Aging Project cohort. Compared with other state-of-art methods, it provided overall the best prediction performance during cross-validation. This new method helped identify a group of densely connected SNPs, genes and proteins predictive of AD status. These SNPs are mostly expression quantitative trait loci in the frontal region. Brain-wide gene expression profile of these genes and proteins were highly correlated with the brain activation map of 'vision', a brain function partly controlled by frontal cortex. These genes and proteins were also found to be associated with the amyloid deposition, cortical ...