Compendium of functional regulatory variants in human neuropsychiatric disease (ATAC-Seq)
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ABSTRACT:
PROVIDER: PRJNA754440 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15446700_1.fastq.gz | Fastqsanger.gz | |||
| SRR15446700_2.fastq.gz | Fastqsanger.gz | |||
| SRR15446701_1.fastq.gz | Fastqsanger.gz | |||
| SRR15446701_2.fastq.gz | Fastqsanger.gz | |||
| SRR15446702_1.fastq.gz | Fastqsanger.gz |
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Project description:Compendium of functional regulatory variants in human neuropsychiatric disease
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Project description:Abstract: Noncoding variants of presumed regulatory function contribute to neuropsychiatric disease heritability. 4442 noncoding variants connected to risk for 10 neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, major depression, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, were studied within developing human neural cells. Integrating epigenomic and transcriptomic data with massively parallel reporter assays identified 637 disease-associated single-nucleotide variants (daSNVs) with altered transcription-regulating activity. Expression-gene mapping, network analyses, and chromatin looping identified 619 candidate disease-relevant target genes modulated by these daSNVs. Specific daSNV-associated molecular pathways mapped to prevalent mental health symptoms. These data provide a framework resource to study inherited pathogenic risk for human neuropsychiatric disorders. Purpose: To place disease-associated single nucleotide variants (daSNVs) in genomic context within human neural cells, matched RNA-seq, chromatin accessibility profiling via ATAC-seq, and enhancer-promoter looping via H3K27ac HiChIP was performed in ES cells and at day 2 (N-D2), 10 (N-D10), and 28 (N-D28) of neuronal differentiation. Additionally, anterior (A-NPC) and posterior (P-NPC) neuronal stem cells were generated and studied. Matched sequencing was also performed on primary human astrocytes from adult brains. Processed and raw data for all cell types can be found in this repository. All biological replicates (n=2) are merged using the ENCODE pipeline.
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Project description:Compendium of functional regulatory variants in human neuropsychiatric disease (HiChIP)
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Project description:Abstract: Noncoding variants of presumed regulatory function contribute to neuropsychiatric disease heritability. 4442 noncoding variants connected to risk for 10 neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, major depression, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, were studied within developing human neural cells. Integrating epigenomic and transcriptomic data with massively parallel reporter assays identified 637 disease-associated single-nucleotide variants (daSNVs) with altered transcription-regulating activity. Expression-gene mapping, network analyses, and chromatin looping identified 619 candidate disease-relevant target genes modulated by these daSNVs. Specific daSNV-associated molecular pathways mapped to prevalent mental health symptoms. These data provide a framework resource to study inherited pathogenic risk for human neuropsychiatric disorders. Purpose: To place disease-associated single nucleotide variants (daSNVs) in genomic context within human neural cells, matched RNA-seq, chromatin accessibility profiling via ATAC-seq, and enhancer-promoter looping via H3K27ac HiChIP was performed in ES cells and at day 2 (N-D2), 10 (N-D10), and 28 (N-D28) of neuronal differentiation. Additionally, anterior (A-NPC) and posterior (P-NPC) neuronal stem cells were generated and studied. Matched sequencing was also performed on primary human astrocytes from adult brains. Processed and raw data for all neural cell types can be found in this repository. Astrocyte raw data can be found at Donohue, et al. "The combinatorial cis-regulatory vocabulary of cell type-specific gene regulation in homeostasis and disease". All biological replicates (n=2) are merged using the ENCODE pipeline.
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Project description:Compendium of functional regulatory variants in human neuropsychiatric disease (MPRA-seq)
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Project description:Compendium of functional regulatory variants in human neuropsychiatric disease (RNA-Seq)
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Project description:Abstract: Noncoding variants of presumed regulatory function contribute to neuropsychiatric disease heritability. 4442 noncoding variants connected to risk for 10 neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, major depression, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, were studied within developing human neural cells. Integrating epigenomic and transcriptomic data with massively parallel reporter assays identified 637 disease-associated single-nucleotide variants (daSNVs) with altered transcription-regulating activity. Expression-gene mapping, network analyses, and chromatin looping identified 619 candidate disease-relevant target genes modulated by these daSNVs. Specific daSNV-associated molecular pathways mapped to prevalent mental health symptoms. These data provide a framework resource to study inherited pathogenic risk for human neuropsychiatric disorders. Purpose: To place disease-associated single nucleotide variants (daSNVs) in genomic context within human neural cells, matched RNA-seq, chromatin accessibility profiling via ATAC-seq, and enhancer-promoter looping via H3K27ac HiChIP was performed in ES cells and at day 2 (N-D2), 10 (N-D10), and 28 (N-D28) of neuronal differentiation. Additionally, anterior (A-NPC) and posterior (P-NPC) neuronal stem cells were generated and studied. Matched sequencing was also performed on primary human astrocytes from adult brains. Processed data for all cell types can be found in this repository. Raw data D10 and D28 RNA seq samples can be found here. Raw data for D0, D2, A-NSC, A-D2, P-NSC, and P-D2 data can be found here: https://www.biorxiv.org/content/10.1101/2020.12.02.398677v1.abstract. Raw data for Astrocytes can be found with the Donohue, et al. "The combinatorial cis-regulatory vocabulary of cell type-specific gene regulation in homeostasis and disease".
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Project description:Abstract: Noncoding variants of presumed regulatory function contribute to neuropsychiatric disease heritability. 4442 noncoding variants connected to risk for 10 neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, major depression, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, were studied within developing human neural cells. Integrating epigenomic and transcriptomic data with massively parallel reporter assays identified 637 disease-associated single-nucleotide variants (daSNVs) with altered transcription-regulating activity. Expression-gene mapping, network analyses, and chromatin looping identified 619 candidate disease-relevant target genes modulated by these daSNVs. Specific daSNV-associated molecular pathways mapped to prevalent mental health symptoms. These data provide a framework resource to study inherited pathogenic risk for human neuropsychiatric disorders. Purpose: To place disease-associated single nucleotide variants (daSNVs) in genomic context within human neural cells, matched RNA-seq, chromatin accessibility profiling via ATAC-seq, and enhancer-promoter looping via H3K27ac HiChIP was performed in ES cells and at day 2 (N-D2), 10 (N-D10), and 28 (N-D28) of neuronal differentiation. Additionally, anterior (A-NPC) and posterior (P-NPC) neuronal stem cells were generated and studied. Matched sequencing was also performed on primary human astrocytes from adult brains. Processed data for all cell types can be found in this repository. Raw data D10 and D28 RNA seq samples can be found here. Raw data for D0, D2, A-NSC, A-D2, P-NSC, and P-D2 data can be found here: https://www.biorxiv.org/content/10.1101/2020.12.02.398677v1.abstract. Raw data for Astrocytes can be found with the Donohue, et al. "The combinatorial cis-regulatory vocabulary of cell type-specific gene regulation in homeostasis and disease".
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2022-12-16 | GSE182095 | GEO
Project description:Mutations in gene regulatory elements have been associated with a wide range of complex neuropsychiatric disorders. However, due to their cell-type specificity and difficulties in characterizing their regulatory targets, the ability to identify causal genetic variants has remained limited. To address these constraints, we perform an integrative analysis of chromatin interactions, open chromatin regions and transcriptomes using promoter capture Hi-C, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing, respectively, in four functionally distinct neural cell types: induced pluripotent stem cell (iPSC)-induced excitatory neurons and lower motor neurons, iPSC-derived hippocampal dentate gyrus-like neurons and primary astrocytes. We identify hundreds of thousands of long-range cis-interactions between promoters and distal promoter-interacting regions, enabling us to link regulatory elements to their target genes and reveal putative processes that are dysregulated in disease. Finally, we validate several promoter-interacting regions by using clustered regularly interspaced short palindromic repeats (CRISPR) techniques in human excitatory neurons, demonstrating that CDK5RAP3, STRAP and DRD2 are transcriptionally regulated by physically linked enhancers.
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