Single-cell transcriptional and epigenomic dissection of Alzheimer's Disease and Related Dementias
阿尔茨海默病和相关痴呆症的单细胞转录和表观基因组解剖
基本信息
- 批准号:10011923
- 负责人:
- 金额:$ 134.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqAddressAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAmyloid beta-ProteinAutopsyBayesian MethodBiologicalBlood VesselsBrainBrain regionCellsClassificationCleaved cellClinicalClinical ManagementClinical TrialsCodeCognitionCognitiveDNADNA-Binding ProteinsDataData SetDefectDementiaDepositionDevelopmentDiagnosticDissectionDistalElderlyEnhancersEvaluationFinancial HardshipFrontotemporal DementiaGene Expression ProfilingGenesGeneticGenetic TranscriptionGenetic VariationHippocampus (Brain)IndividualInjuryLewy BodiesLewy Body DementiaLinkMapsMediationMemoryMolecularMolecular ProfilingMutationNeurofibrillary TanglesNeurologicNucleic Acid Regulatory SequencesPathologicPathway interactionsPersonalityPhenotypePlayPrefrontal CortexPublic HealthResourcesRoleSamplingSenile PlaquesSeveritiesSeverity of illnessSocial BehaviorStrokeTechniquesTechnologyTherapeutic InterventionTransactTransposaseUntranslated RNAVariantalpha synucleinbasecell typecohortdifferential expressionepigenomicsextracellulargene discoverygenetic informationgenome sequencinggenome wide association studygenome-widehealthy aginginsightnew therapeutic targetnovel therapeuticsprognosticrare variantreligious order studyresponsesexsingle-cell RNA sequencingsocialtau Proteinstherapeutic developmenttherapeutic targettraittranscriptomicsvascular cognitive impairment and dementiawhole genome
项目摘要
Dementia is a major public health problem with substantial personal, social, and financial burden, affecting more than 47 million people worldwide, with no cure to date. The major types of dementia include Alzheimer’s disease (AD), Lewy Body dementia (LBD), and frontotemporal dementia (FTD), which show distinct and overlapping pathological, neurological, and cellular signatures, but their detailed molecular signatures remain uncharacterized. Here, we systematically profile the molecular signatures of AD, LBD, FTD, and healthy aging, at the single-cell level, across traits, individuals, brain regions, cell types, age, sex, and disease severity. We use genetic, epigenomic, and transcriptional profiles, generating a total of ~1.5 million genome-wide maps at the single-cell (sc) level using scRNA-seq and scATAC-seq across 768 post-mortem brain samples from the Religious Order Study and Memory and Aging Project (ROS MAP) cohorts. We analyze the resulting datasets in the context of genetic variation from whole-genome sequencing, and phenotypic variation from rich longitudinal profiling and cognitive evaluations, enabling us to discover genes, control regions, pathways, cell types, and brain regions playing causal roles in AD and ADRD, and how they vary across age, sex, and traits. The resulting datasets will help guide the search for new therapeutics, by providing detailed therapeutic targets, and the specific conditions where they are predicted to act.
痴呆症是一个重大的公共卫生问题,具有重大的个人、社会和经济负担,影响着全世界4700多万人,迄今尚无治愈方法。痴呆的主要类型包括阿尔茨海默病(AD)、路易体痴呆(LBD)和额颞叶痴呆(FTD),它们表现出不同且重叠的病理、神经和细胞特征,但其详细的分子特征仍未被表征。在这里,我们系统地分析了AD、LBD、FTD和健康衰老的分子特征,在单细胞水平上,跨越特征、个体、大脑区域、细胞类型、年龄、性别和疾病严重程度。我们使用遗传、表观基因组和转录谱,利用scRNA-seq和scATAC-seq在单细胞(sc)水平上生成了大约150万个全基因组图谱,这些图谱来自宗教秩序研究和记忆与衰老项目(ROS MAP)队列的768个死后大脑样本。我们在全基因组测序的遗传变异背景下分析所得数据集,并从丰富的纵向分析和认知评估中分析表型变异,使我们能够发现在AD和ADRD中起因果作用的基因,控制区,途径,细胞类型和大脑区域,以及它们如何在年龄,性别和性状中变化。由此产生的数据集将通过提供详细的治疗靶点和预测它们起作用的具体条件,帮助指导寻找新的治疗方法。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Manolis Kellis其他文献
Manolis Kellis的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Manolis Kellis', 18)}}的其他基金
Investigating cell-type specific convergence of APOE and ABCA7 lipid dysregulation in Alzheimer’s disease
研究阿尔茨海默病中 APOE 和 ABCA7 脂质失调的细胞类型特异性趋同
- 批准号:
10900993 - 财政年份:2023
- 资助金额:
$ 134.54万 - 项目类别:
Single-cell multi-region dissection of AD-pathogen interactions for HSV-1 and CMV
HSV-1 和 CMV AD 病原体相互作用的单细胞多区域解剖
- 批准号:
10607814 - 财政年份:2023
- 资助金额:
$ 134.54万 - 项目类别:
Single-cell epigenomic and trancriptional dissection of sex-specific differences in Alzheimer’s Disease
阿尔茨海默病性别特异性差异的单细胞表观基因组和转录解析
- 批准号:
10495202 - 财政年份:2021
- 资助金额:
$ 134.54万 - 项目类别:
Single-cell epigenomic and trancriptional dissection of sex-specific differences in Alzheimer’s Disease
阿尔茨海默病性别特异性差异的单细胞表观基因组和转录解析
- 批准号:
10300867 - 财政年份:2021
- 资助金额:
$ 134.54万 - 项目类别:
Single-cell epigenomic and trancriptional dissection of sex-specific differences in Alzheimer’s Disease
阿尔茨海默病性别特异性差异的单细胞表观基因组和转录解析
- 批准号:
10633255 - 财政年份:2021
- 资助金额:
$ 134.54万 - 项目类别:
Single-cell transcriptional and epigenomic dissection of Alzheimer's Disease and Related Dementias
阿尔茨海默病和相关痴呆症的单细胞转录和表观基因组解剖
- 批准号:
9791035 - 财政年份:2018
- 资助金额:
$ 134.54万 - 项目类别:
Elucidating the Molecular Mechanisms of Neuropsychiatric Symptoms in Alzheimer's Disease
阐明阿尔茨海默病神经精神症状的分子机制
- 批准号:
10451516 - 财政年份:2018
- 资助金额:
$ 134.54万 - 项目类别:
Elucidating the Molecular Mechanisms of Neuropsychiatric Symptoms in Alzheimer's Disease
阐明阿尔茨海默病神经精神症状的分子机制
- 批准号:
10177837 - 财政年份:2018
- 资助金额:
$ 134.54万 - 项目类别:
Interpreting non-coding variants using epigenomics, regulatory models, & validation experiments
使用表观基因组学、调控模型解释非编码变异,
- 批准号:
9616350 - 财政年份:2017
- 资助金额:
$ 134.54万 - 项目类别:
Interpreting non-coding variants using epigenomics, regulatory models, & validati
使用表观基因组学、调控模型解释非编码变异,
- 批准号:
9349567 - 财政年份:2015
- 资助金额:
$ 134.54万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 134.54万 - 项目类别:
Research Grant