Integrative analysis of high dimensional tissue molecular data to define key biological systems in autoimmune diseases (SBC)
高维组织分子数据综合分析,定义自身免疫性疾病 (SBC) 的关键生物系统
基本信息
- 批准号:10450354
- 负责人:
- 金额:$ 30万
- 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:2022-03-18 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
PROJECT SUMMARY/ABSTRACT
Here we propose a Systems Biology Core (SBC) for the Accelerating Medicines Partnerships in Autoimmune
and Immune-Mediated Diseases (AMP AIM). The AMP AIM will use high dimensional molecular and cellular
assays to define the key cell states, pathways, and molecular components of tissue inflammation and damage
by examining patient tissue and blood samples. Ultimately, we seek to define the components of tissue
inflammation in autoimmune and inflammatory diseases including psoriatic spectrum diseases (PSD),
rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), and other related
conditions. AMP RA/SLE initiated this process by querying 106 single cells in inflamed RA synovial and SLE
nephritis tissue samples using multimodal strategies; it defined key cell states in tissue inflammation, including
T peripheral helper T cells (Tph), GZMK+ CD8+ T cells, HLA-DR+THY1+ fibroblasts, and autoimmune-
associated B cells (ABCs). Now, to understand how these and emerging cell-states function and interact to
cause disease, it will be essential to obtain high dimensional data on patient sample data across a spectrum of
diseases and disease sub-phenotypes. These data may capture the cellular states; the spatial localization of
cell states, proteins and transcripts; histological features; and other tissue parameters. A powerful and skilled
team that is able to define strategies to analyze this data, integrate multiple modalities of data, and integrate
results from across a diverse set of diseases and tissues will be essential to the success of this program.
We build from our experience leading the Systems Biology Group within the Accelerating Medicines
Partnerships Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE). We have built a team
that is skilled at analysis of diverse modalities and computational biology. We have specific experience and
expertise in inflammatory diseases. Here we propose to:
(1) Develop Tools and Technology to analyze high dimensional cellular and molecular data. This includes
optimizing existing bioinformatics and computational tools. It also includes developing new
computational and statistical methods to integrate high dimensional data manifestation of disease.
(2) Enable collaboration throughout the network and facilitate systems level analysis. We envision that this
is an integrated activity with the network, where we will devise and ultimately create an integrated
model of tissue inflammation across diseases to define features that drive clinical disease. This will
require the development of new statistical and computational methods. It will also require tight
collaboration within the network including data synchronization, storage, sharing, and clinical data
integration. In addition, we will engage the network by offering consultation, technical support and
training in high dimensional data analysis.
.
项目摘要/摘要
在这里,我们提出了一个系统生物学核心(SBC),用于自动免疫的加速药物合作伙伴关系
和免疫介导的疾病(AMP AIM)。 AMP AIM将使用高维分子和细胞
定义组织注射和损伤的关键细胞状态,途径和分子成分的测定法
通过检查患者组织和血液样本。最终,我们试图定义组织的组成部分
自身免疫性和炎症性疾病的炎症,包括银屑病谱系疾病(PSD),
类风湿关节炎(RA),全身性红斑狼疮(SLE),Sjogren综合征(SS)和其他相关的
状况。 AMP RA/SLE通过在发炎的RA滑膜和SLE中查询106个单细胞来启动此过程
使用多模式策略的肾炎组织样品;它在组织注射中定义了关键细胞态,包括
T外围帮助者T细胞(TPH),GZMK+ CD8+ T细胞,HLA-DR+ THY1+成纤维细胞和自身免疫性 -
相关的B细胞(ABC)。现在,了解这些和新兴的细胞态如何运作并与
导致疾病,至关重要的
疾病和疾病亚表征。这些数据可能捕获细胞状态;空间本地化
细胞状态,蛋白质和转录本;组织学特征;和其他组织参数。一个强大而熟练的
能够定义策略来分析这些数据,集成了多种数据模式并集成的团队
从潜水员组成的一组疾病和组织的结果对于该计划的成功至关重要。
我们从领导系统生物学小组的经验中建立在加速药物中
伴侣类风湿关节炎和全身性红斑狼疮(AMP RA/SLE)。我们已经建立了一个团队
这是对潜水模式和计算生物学分析的熟练分析。我们有特定的经验,
炎症性疾病的专业知识。在这里,我们建议:
(1)开发工具和技术来分析高维细胞和分子数据。这包括
优化现有的生物信息学和计算工具。它还包括开发新的
整合疾病的高维数据表现的计算和统计方法。
(2)在整个网络中启用协作,并促进系统级分析。我们设想这个
是与网络的集成活动,我们将在其中设计并最终创建一个集成的活动
跨疾病的组织炎症模型,以定义驱动临床疾病的特征。这会
需要开发新的统计和计算方法。它也需要紧身
网络内的协作包括数据同步,存储,共享和临床数据
此外,我们将通过提供咨询,技术支持和
高维数据分析中的培训。
。
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)

暂无数据
数据更新时间:2024-06-01
Soumya Raychaudhu...的其他基金
Integrative analysis of high dimensional tissue molecular data to define key biological systems in autoimmune diseases (SBC)
高维组织分子数据综合分析,定义自身免疫性疾病 (SBC) 的关键生物系统
- 批准号:1068772810687728
- 财政年份:2022
- 资助金额:$ 30万$ 30万
- 项目类别:
Integrative analysis of high dimensional tissue molecular data to define key biological systems in autoimmune diseases (SBC)
高维组织分子数据综合分析,定义自身免疫性疾病 (SBC) 的关键生物系统
- 批准号:1059450510594505
- 财政年份:2022
- 资助金额:$ 30万$ 30万
- 项目类别:
Defining the influence of RA genetic susceptibility factors on T cell antigen specificity and functional state
定义 RA 遗传易感因素对 T 细胞抗原特异性和功能状态的影响
- 批准号:1021080610210806
- 财政年份:2013
- 资助金额:$ 30万$ 30万
- 项目类别:
Defining the influence of RA genetic susceptibility factors on T cell antigen specificity and functional state
定义 RA 遗传易感因素对 T 细胞抗原特异性和功能状态的影响
- 批准号:1041496410414964
- 财政年份:2013
- 资助金额:$ 30万$ 30万
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Discovery and Functional Impact of Common and Rare Variants in RA
RA 常见和罕见变异的发现及其功能影响
- 批准号:87123638712363
- 财政年份:2013
- 资助金额:$ 30万$ 30万
- 项目类别:
Discovery and Functional Impact of Common and Rare Variants in RA
RA 常见和罕见变异的发现及其功能影响
- 批准号:94785469478546
- 财政年份:2013
- 资助金额:$ 30万$ 30万
- 项目类别:
Discovery and Functional Impact of Common and Rare Variants in RA
RA 常见和罕见变异的发现及其功能影响
- 批准号:85762068576206
- 财政年份:2013
- 资助金额:$ 30万$ 30万
- 项目类别:
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