Integrated, cell type specific functional genomics analyses of regulatory sequence elements and their dynamic interaction networks in neuropsychiatric brain tissues
神经精神脑组织中调节序列元件及其动态相互作用网络的综合、细胞类型特异性功能基因组学分析
基本信息
- 批准号:10609543
- 负责人:
- 金额:$ 164.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-20 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalATAC-seqAdultAllelesAutopsyBiological AssayBipolar DisorderBrainBrain regionCell FractionCell NucleusCellsChromatinChromosome MappingChromosomesCodeCopy Number PolymorphismCoupledCritical PathwaysDNADNA mappingDataData AnalysesDatabasesDevelopmentDimensionsDiseaseDisease MarkerDisease PathwayEarly DiagnosisEarly InterventionElementsFreezingFutureGene Expression ProfileGeneticGenetic DiseasesGenetic TranscriptionGenomeGenomicsGoalsHaplotypesHumanHuman DevelopmentHuman GenomeIndividualKnowledgeLinkLongevityMapsMass Spectrum AnalysisMental disordersNatureNeurogliaNeuronsNuclearNuclear ProteinNuclear ProteinsNucleic Acid Regulatory SequencesOrganoidsPathologyPathway interactionsPatientsPatternPhasePreventive careProteomicsRegional AnatomySamplingSchizophreniaSeriesSortingSourceStretchingTechniquesTechnologyTimeTissuesUntranslated RNAVariantautism spectrum disorderbioinformatics toolbrain tissuecell typeclinical phenotypecomplex datacomputational pipelinesdata integrationdesignepigenomicsfetalfunctional genomicsgenetic architectureinduced pluripotent stem cellinnovationmind controlneuralneuropsychiatric disorderneuropsychiatrynovelprenatalpsychiatric genomicspsychogeneticsrare variantsingle-cell RNA sequencingtranscription factortranscriptometranscriptome sequencingwhole genome
项目摘要
Project Summary/Abstract
After a century of debate about the fundamental nature of neuropsychiatric disorders, we know that genetics lie
at their core, yet do not fully understand the critical underlying mechanisms of their disease-causing pathology.
The overall goal of our proposal is the creation of comprehensive and integrated maps of chromatin
accessibility, chromosome folding and transcriptional patterns, delineating regulatory regions in the genomes
of key disease relevant anatomical regions of adult and fetal brains, in brains from patients with Schizophrenia,
Autism Spectrum Disorder, Bipolar Affective Disorder and matched controls, and those with known CNVs
(Copy-Number Variants) that may unmask regional or long-range targets of epigenomic regulatory interactions
that may also be of great relevance in patients with the same clinical phenotype. We will use comprehensive
and highly-resolving epigenomics assays, that were recently developed by us, and novel ways to integrate the
data for the first time in neuropsychiatrically relevant brain tissues. We will generate comprehensive maps of
the spectrum of organization and function of regulatory regions by integrating complementary techniques:
single-cell ATAC-seq (scATAC-seq) to characterize chromatin openness and HiChIP to characterize long-
range folding interactions of sorted neuronal and non-neuronal cells, both of which are coupled to single-cell
RNA-seq and long-range RNA-seq for expression information, further complimented by information about
transcription factors through proteomic analysis of nuclear fractions. These maps will then be combined with
coding or non-coding/regulatory variants in the genomic sequence in the candidate regions and integrated into
the overall PsychENCODE database, which will allow us to create and validate reference maps for epigenomic
marks and interactions, determine aberrations to the reference state in patient tissue, and connect such
aberrations to genetic disease loci as well as assemble such loci into disease pathways. This project will not
only greatly expand our understanding of regulatory information encoded in the human genome and its impact
on human brain development and neuropsychiatric disorders, but also produce the bioinformatics tools
necessary to analyze the complex data being generated in PsychENCODE.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOACHIM F HALLMAYER其他文献
JOACHIM F HALLMAYER的其他文献
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{{ truncateString('JOACHIM F HALLMAYER', 18)}}的其他基金
Integrated, cell type specific functional genomics analyses of regulatory sequence elements and their dynamic interaction networks in neuropsychiatric brain tissues
神经精神脑组织中调节序列元件及其动态相互作用网络的综合、细胞类型特异性功能基因组学分析
- 批准号:
10411895 - 财政年份:2019
- 资助金额:
$ 164.33万 - 项目类别:
Integrated, cell type specific functional genomics analyses of regulatory sequence elements and their dynamic interaction networks in neuropsychiatric brain tissues
神经精神脑组织中调节序列元件及其动态相互作用网络的综合、细胞类型特异性功能基因组学分析
- 批准号:
10133146 - 财政年份:2019
- 资助金额:
$ 164.33万 - 项目类别:
Gene expression profiling of IPSC derived neurons in Autism Spectrum Disorder
自闭症谱系障碍中 IPSC 衍生神经元的基因表达谱
- 批准号:
10320346 - 财政年份:2018
- 资助金额:
$ 164.33万 - 项目类别:
Creation and Evaluation of iPSCs from Children with ASD with Megalencephaly
自闭症谱系障碍 (ASD) 巨脑畸形儿童 iPSC 的创建和评估
- 批准号:
10238008 - 财政年份:2017
- 资助金额:
$ 164.33万 - 项目类别:
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