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An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease (RNA-seq) [RNA-seq]

ABSTRACT: We report the bulk RNA-seq in human hippocampus subject to normal aging and Alzheimer's disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159699 | GEO | 2020/10/21

REPOSITORIES: GEO

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An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease (5hmC) [5hmC-Seal]

Project description:We report the 5hmC in human hippocampus subject to normal aging and Alzheimer's disease.

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An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease (RNA-seq with ERCC spike-in) [RNA-Seq]

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An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease (H3K9ac, H3K27ac, H3K122ac, H3K4me1) [ChIP-Seq]

Project description:We report the epigenetic landscape of multiple histone marks in human hippocampus subject to normal aging and Alzheimer's disease.

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An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-07 | GSE153875 | GEO

An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer's disease.

Project description:Protein aggregation is the hallmark of neurodegeneration, but the molecular mechanisms underlying late-onset Alzheimer's disease (AD) are unclear. Here we integrated transcriptomic, proteomic and epigenomic analyses of postmortem human brains to identify molecular pathways involved in AD. RNA sequencing analysis revealed upregulation of transcription- and chromatin-related genes, including the histone acetyltransferases for H3K27ac and H3K9ac. An unbiased proteomic screening singled out H3K27ac and H3K9ac as the main enrichments specific to AD. In turn, epigenomic profiling revealed gains in the histone H3 modifications H3K27ac and H3K9ac linked to transcription, chromatin and disease pathways in AD. Increasing genome-wide H3K27ac and H3K9ac in a fly model of AD exacerbated amyloid-β42-driven neurodegeneration. Together, these findings suggest that AD involves a reconfiguration of the epigenome, wherein H3K27ac and H3K9ac affect disease pathways by dysregulating transcription- and chromatin-gene feedback loops. The identification of this process highlights potential epigenetic strategies for early-stage disease treatment.

| S-EPMC8098004 | biostudies-literature

An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease

Project description:An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease

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Integrated multi-omics approach revealed cellular senescence landscape.

Project description:Cellular senescence is a complex multifactorial biological phenomenon that plays essential roles in aging, and aging-related diseases. During this process, the senescent cells undergo gene expression altering and chromatin structure remodeling. However, studies on the epigenetic landscape of senescence using integrated multi-omics approaches are limited. In this research, we performed ATAC-seq, RNA-seq and ChIP-seq on different senescent types to reveal the landscape of senescence and identify the prime regulatory elements. We also obtained 34 key genes and deduced that NAT1, PBX1 and RRM2, which interacted with each other, could be the potential markers of aging and aging-related diseases. In summary, our work provides the landscape to study accessibility dynamics and transcriptional regulations in cellular senescence. The application of this technique in different types of senescence allows us to identify the regulatory elements responsible for the substantial regulation of transcription, providing the insights into molecular mechanisms of senescence.

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An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease (RNA-seq) [RNA-seq]

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Prediction of gene activity based on an integrated multi-omics approach.

Project description:An increasingly common method for predicting gene activity is genome-wide chromatin immunoprecipitation of M-bM-^@M-^XactiveM-bM-^@M-^Y chromatin modifications followed by massively parallel sequencing (ChIP-seq). Using a novel ChIP-seq quantification method (cRPKM), we tested the power of such ChIP-seq strategies to predict relative protein and RNA levels at the pre-pro-B and pro-B differentiation stages in early B cell lymphopoiesis. Using a multi-omics approach that compares promoter chromatin status (ChIP-seq; published in GSE:21978) with ongoing active transcription (GRO-seq; published in GSE:40173), steady state mRNA (RNA-seq), inferred mRNA stability, and relative proteome abundance measurements (iTRAQ), we demonstrate that active chromatin modifications at promoters are a good indicator of transcription and steady state mRNA levels. Moreover, we found that promoters with active chromatin modifications exclusively in one of these cell states frequently predicted differentially expressed proteins. However, we found that many genes whose promoters have non-differential but active chromatin modifications also displayed changes in expression of their cognate proteins. This large class of developmentally and differentially regulated proteins that was uncoupled from chromatin status used mostly post-transcriptional mechanisms. Interestingly, the most differentially expressed protein in our B-cell development system, 2410004B18Rik, was regulated by a post-transcriptional mechanism, which further analyses indicated was mediated by an identified miRNA. These data provide a striking example of how our integrated multi-omics data set can be useful in uncovering regulatory mechanisms. Total RNA from mouse pre-pro-B and pro-B cells, depleted of rRNA and small RNAs, was sequenced using a strand specific, single end sequencing strategy.

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