2020
DOI: 10.1371/journal.pcbi.1007771
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Bayesian integrative analysis of epigenomic and transcriptomic data identifies Alzheimer's disease candidate genes and networks

Abstract: Biomedical research studies have generated large multi-omic datasets to study complex diseases like Alzheimer's disease (AD). An important aim of these studies is the identification of candidate genes that demonstrate congruent disease-related alterations across the different data types measured by the study. We developed a new method to detect such candidate genes in large multi-omic case-control studies that measure multiple data types in the same set of samples. The method is based on a gene-centric integra… Show more

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Cited by 14 publications
(17 citation statements)
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References 114 publications
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“…spatial transcriptomics (Chen et al 2020;Prokop et al 2019) with multi-omics approaches i.e. epigenomics, proteomics and metabolomics (Johnson et al 2020;Klein et al 2020;Swarup et al 2020) will allow validation of the present findings and provide specific mechanisms for therapeutic intervention. Table 1.…”
Section: Astrocyte Genes and Altered Molecular Pathways In Admentioning
confidence: 80%
“…spatial transcriptomics (Chen et al 2020;Prokop et al 2019) with multi-omics approaches i.e. epigenomics, proteomics and metabolomics (Johnson et al 2020;Klein et al 2020;Swarup et al 2020) will allow validation of the present findings and provide specific mechanisms for therapeutic intervention. Table 1.…”
Section: Astrocyte Genes and Altered Molecular Pathways In Admentioning
confidence: 80%
“…Although there is still an acute need for more in-depth RNA sequencing analyses combined with large-scale meta-analyses on astrocyte transcriptomic datasets [ 144 ], the identification of genes and transcription factors that orchestrate the conversion of control to AD-associated astrocytes can already pinpoint specific molecular processes. In the coming years, integration of the most advanced sequencing technologies i.e., spatial transcriptomics [ 145 , 146 ] with multi-omics approaches i.e., epigenomics, proteomics and metabolomics [ 147 , 148 , 149 ] will allow validation of the present findings and provide specific mechanisms for therapeutic intervention.…”
Section: Astrocytes In Alzheimer’s Diseasementioning
confidence: 99%
“…The fact that at least two such associations-in ABCA7 and BIN1-occur in loci that are genetically validated as AD susceptibility loci but are not explained by the AD risk allele enhances our confidence that risk factors may converge on certain proteins through different molecular effects. Indeed, this observation of multi-omic convergence has been leveraged to find loci associated with residual cognition where genetic, DNA methylation and transcriptomic associations converge (42) and, in another case, to systematically aggregate evidence of association with AD in four layers of omic data from the same individuals (19).…”
Section: A Variety Of Multi-omic Approachesmentioning
confidence: 99%
“…Generally, however, the prediction accuracy of these approaches remain largely unknown and have to be assessed by future studies. Finally, one recent effort used a Bayesian effort to summarize evidence of AD associations across two dimensions of epigenomic data and paired transcriptomic data from the same individuals; this yielded a set of candidates that were validated using proteomic data and could be assembled into networks that captured known biology, including dysfunction of myeloid cell networks (19).…”
Section: Designing a Well-powered Study Of The Aging Brain By Leveragmentioning
confidence: 99%