Identifying the organotypic and disease-specific vascular cell populations by integrating single cell data with polygenic risk
通过将单细胞数据与多基因风险相结合来识别器官型和疾病特异性血管细胞群
基本信息
- 批准号:10852399
- 负责人:
- 金额:$ 8.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAortaBiologyBlood VesselsCellsCollectionCommunitiesComputational BiologyComputer softwareComputing MethodologiesCoronary ArteriosclerosisDataData SetDementiaDiabetes MellitusDiseaseDisease ProgressionEndothelial CellsGenesGeneticGenetic RiskGenetic TranscriptionHeterogeneityHumanHuman BioMolecular Atlas ProgramHuman bodyLinkMalignant NeoplasmsMethodologyMethodsMorbidity - disease rateMusMyofibroblastOrganPathway interactionsPlayPopulationProcessResearch PersonnelRiskRoleSamplingSmooth Muscle MyocytesSourceStrokeTissuesUnited StatesVascular DiseasesVascular Smooth Musclecell typedata integrationdata sharingdisorder riskgenetic associationgenome wide association studymortalityopen dataprogramspublic health relevancesexsingle cell analysissingle nucleus RNA-sequencingsingle-cell RNA sequencing
项目摘要
Vascular cells are present throughout the human body and contribute to risk of multiple diseases.
Vascular dysfunction directly affects risk for arterial diseases (e.g. coronary artery disease and stroke) as well
as manifestations of other diseases such as dementia, cancer, and diabetes. Single cell analysis of the human
vasculature has already begun to identify the basic mechanisms of vascular dysfunction in the large number of
associated diseases. Our group, and several other labs, have used single cell RNA-sequencing (scRNA-seq) to
identify vascular cell heterogeneity. We performed scRNA-seq of the aorta to identify functionally distinct
endothelial cell (EC) subpopulations, and multiple groups have identified activated myofibroblasts in diseased
mouse and human vascular tissue. These studies prove heterogenous cell populations exist in the arterial wall,
but it remains undetermined which populations play a causal role in early vascular dysfunction and disease risk.
The Human BioMolecular Atlas Program (HuBMAP) provides a rich source of data to begin to establish
a causal link for specific vascular cell subpopulations with disease. In HuBMAP data, ECs and vascular smooth
muscle cells (VSMCs) comprise a large portion of the single cells identified from each organ. However, to
establish the cell types and transcriptional pathways associated with disease it will be necessary to incorporate
the new datasets and computational methods we propose in this application. We aim to use new computational
methods to integrate data from diseased vascular tissue with normal HuBMAP data, to identify the disease-
relevant features of vascular cells. New methods to integrate disease associated genes from GWAS will also
help investigators prioritize causal cells for multiple common diseases. To achieve this, we will: 1) Use new
software to identify organotypic features of vascular cells in HUBMAP reference data; 2) Identify disease-specific
vascular cell signature by comparing HUBMAP reference data with samples from vascular disease; and 3) Build
and share a computational program to identify disease-relevant cell populations and gene modules through
integration with genetic association data. These analyses make use of existing vascular disease snRNA-seq
data from a rich collection of diseased subjects we can share with the HuBMAP. All data from vascular disease
subjects is available for open data sharing, and has been collected to include a diverse collection of subjects
with respect to sex and ancestry. Our methods and statistical software to perform this integration of multiple
single cell datasets with genetic associations will establish a generalizable methodology to rapidly discover the
disease-relevant cells and processes of the vasculature, and all other cell-types, for any diseases with genetic
risk and available GWAS. Our team is immediately ready to undertake the proposed studies and share the
software with the HuBMAP community. We have a track record of rapidly sharing single cell RNA-seq data, and
have a diverse team with expertise in vascular biology, statistical genetics, and computational biology.
血管细胞存在于整个人体中,并导致多种疾病的风险。
血管功能障碍也直接影响动脉疾病(如冠状动脉疾病和中风)的风险
作为其他疾病的表现,如痴呆症,癌症和糖尿病。人的单细胞分析
血管系统已经开始在大量的血管疾病中确定血管功能障碍的基本机制。
相关疾病。我们的团队和其他几个实验室已经使用单细胞RNA测序(scRNA-seq)来
鉴定血管细胞异质性。我们对主动脉进行了scRNA-seq,
内皮细胞(EC)亚群,多个研究小组已经在病变组织中鉴定出活化的肌成纤维细胞。
小鼠和人类血管组织。这些研究证明了动脉壁中存在异质性细胞群,
但仍不确定哪些人群在早期血管功能障碍和疾病风险中起因果作用。
人类生物分子图谱计划(HuBMAP)为开始建立
特定血管细胞亚群与疾病的因果关系。在HuBMAP数据中,EC和血管平滑
肌细胞(VSMC)包括从每个器官鉴定的大部分单细胞。但要
建立与疾病相关的细胞类型和转录途径,
我们在本申请中提出的新数据集和计算方法。我们的目标是使用新的计算
将来自患病血管组织的数据与正常HuBMAP数据整合的方法,以识别疾病-
血管细胞的相关特征。整合来自GWAS的疾病相关基因的新方法也将
帮助研究人员优先考虑多种常见疾病的致病细胞。为了实现这一目标,我们将:1)使用新的
用于识别HUBMAP参考数据中血管细胞器官型特征的软件; 2)识别疾病特异性
通过比较HUBMAP参考数据与来自血管疾病的样品的血管细胞特征;以及3)构建
并共享一个计算程序来识别疾病相关的细胞群和基因模块,
与遗传关联数据的整合。这些分析利用现有的血管疾病snRNA-seq
我们可以与HuBMAP分享来自丰富的患病受试者的数据。血管疾病的所有数据
受试者可用于开放数据共享,并已收集到包括不同受试者的集合
在性别和血统方面。我们的方法和统计软件来执行这种多个
具有遗传关联的单细胞数据集将建立一种可推广的方法,以快速发现
疾病相关的细胞和脉管系统的过程,以及所有其他细胞类型,对于任何具有遗传性的疾病,
风险和可用的GWAS。我们的团队立即准备进行拟议的研究,并分享
HuBMAP社区的软件。我们有快速共享单细胞RNA-seq数据的记录,
我们拥有一支多元化的团队,拥有血管生物学、统计遗传学和计算生物学方面的专业知识。
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 }}
RAJAT M GUPTA其他文献
RAJAT M GUPTA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('RAJAT M GUPTA', 18)}}的其他基金
Identifying the organotypic and disease-specific vascular cell populations by integrating single cell data with polygenic risk
通过将单细胞数据与多基因风险相结合来识别器官型和疾病特异性血管细胞群
- 批准号:
10652639 - 财政年份:2022
- 资助金额:
$ 8.96万 - 项目类别:
Identifying the organotypic and disease-specific vascular cell populations by integrating single cell data with polygenic risk
通过将单细胞数据与多基因风险相结合来识别器官型和疾病特异性血管细胞群
- 批准号:
10530959 - 财政年份:2022
- 资助金额:
$ 8.96万 - 项目类别:
A genetic approach to identify the common mechanisms of vascular disease
识别血管疾病常见机制的遗传学方法
- 批准号:
10477676 - 财政年份:2019
- 资助金额:
$ 8.96万 - 项目类别:
Single cell analysis of gene expression in human vascular cells
人类血管细胞基因表达的单细胞分析
- 批准号:
9810454 - 财政年份:2019
- 资助金额:
$ 8.96万 - 项目类别:
From association to function at the PHACTR1 GWAS locus for coronary atherosclerosis
PHACTR1 GWAS 位点与冠状动脉粥样硬化的关联和功能
- 批准号:
9919442 - 财政年份:2019
- 资助金额:
$ 8.96万 - 项目类别:
From association to function at the PHACTR1 GWAS locus for coronary atherosclerosis
PHACTR1 GWAS 位点与冠状动脉粥样硬化的关联和功能
- 批准号:
10004934 - 财政年份:2019
- 资助金额:
$ 8.96万 - 项目类别:
From association to function at the PHACTR1 GWAS locus for coronary atherosclerosis
PHACTR1 GWAS 位点与冠状动脉粥样硬化的关联和功能
- 批准号:
9298804 - 财政年份:2016
- 资助金额:
$ 8.96万 - 项目类别:
From association to function at the PHACTR1 GWAS locus for coronary atherosclerosis
PHACTR1 GWAS 位点与冠状动脉粥样硬化的关联和功能
- 批准号:
9263835 - 财政年份:2016
- 资助金额:
$ 8.96万 - 项目类别:
相似海外基金
Deep learning to enable the genetic analysis of aorta
深度学习可实现主动脉的遗传分析
- 批准号:
10807379 - 财政年份:2023
- 资助金额:
$ 8.96万 - 项目类别:
Clinical benefits and mechanism of action of angiotensin-II receptor blocker on Cardiovascular remodeling in patients with repaired coarctation of aorta
血管紧张素II受体阻滞剂对主动脉缩窄修复患者心血管重塑的临床疗效及作用机制
- 批准号:
10734120 - 财政年份:2023
- 资助金额:
$ 8.96万 - 项目类别:
Development of new preventive method for postoperative paraplegia of thoracoabdominal aorta using exosomes
利用外泌体开发胸腹主动脉术后截瘫的新预防方法
- 批准号:
22K08940 - 财政年份:2022
- 资助金额:
$ 8.96万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CAREER: Hemodynamic Mechanisms of Heart-Aorta-Brain Coupling with An Integrated Preventive Medicine Education Program for Socioeconomically Disadvantaged Groups
职业:心-主动脉-脑耦合的血流动力学机制以及针对社会经济弱势群体的综合预防医学教育计划
- 批准号:
2145890 - 财政年份:2022
- 资助金额:
$ 8.96万 - 项目类别:
Continuing Grant
Dissecting the role of hemodynamics in ascending aorta aneurysm development in bicuspid aortic valve disease
剖析血流动力学在二叶式主动脉瓣疾病升主动脉瘤发展中的作用
- 批准号:
500274 - 财政年份:2022
- 资助金额:
$ 8.96万 - 项目类别:
Studentship Programs
Smooth muscle cell diversity and thoracic aorta vulnerability
平滑肌细胞多样性和胸主动脉脆弱性
- 批准号:
453372 - 财政年份:2021
- 资助金额:
$ 8.96万 - 项目类别:
Operating Grants
Deep learning to enable the genetic analysis of aorta
深度学习可实现主动脉的遗传分析
- 批准号:
10613402 - 财政年份:2021
- 资助金额:
$ 8.96万 - 项目类别:
Development of bifurcated curved bio-tube for the aorta with in-body tissue architecture
开发具有体内组织结构的主动脉分叉弯曲生物管
- 批准号:
21H03819 - 财政年份:2021
- 资助金额:
$ 8.96万 - 项目类别:
Grant-in-Aid for Scientific Research (B)