Data Core

数据核心

基本信息

批准号：
10806551
负责人：
Mingyao Li
金额：
$ 76.5万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10806551
关键词：
Address Affect Afferent Neurons Alternative Splicing Bioconductor Bioinformatics Biology Biometry Categories Cell Communication Cell Nucleus Cells Chromatin Code Collaborations Communities Complex Computational Biology Data Data Analyses Data Provenance Data Set Data Storage and Retrieval Detection Development Documentation Ensure Epigenetic Process Evaluation Excision Experimental Designs Facial Pain Formulation Fostering Foundations Gene Expression Genes Goals Head Headache Disorders Helping to End Addiction Long-term Household Human Human Resources International Knowledge Knowledge Management Length Link Maps Mediating Metadata Methods Methylation Migraine Modality Modernization Molecular Multiomic Data Neurons Pain Pain Clinics Pathway Analysis Performance Physiological Protein Isoforms Quality Control Reproducibility Research Research Design Research Personnel Research Project Grants Resolution Sample Size Small Nuclear RNA Spinal Ganglia Statistical Computing Statistical Methods Structure Structure of trigeminal ganglion Tissue-Specific Gene Expression Transcript Trigeminal System United States National Institutes of Health Work allodynia analysis pipeline cell type chronic painful condition computerized tools data centers data harmonization data hub data integration data management data quality data sharing data submission design effective therapy experimental study human RNA sequencing human data migraine treatment multidisciplinary multiple omics nervous system disorder neuronal cell body novel programs repository response single cell analysis single-cell RNA sequencing somatosensory sound tool transcriptome transcriptomic profiling transcriptomics

项目摘要

Migraine, one of the most common primary headache disorders, affects 1 in 4 US households. This complex neurologic disorder is mediated in part by alterations in trigeminal somatosensation, which manifests as head/fa- cial pain and/or trigeminal allodynia. Effective treatments for migraine are still limited, and our knowledge about human trigeminal system at baseline and migraine conditions are sparse. In response to RFA-NS-22-018, HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes & Cells, we propose to form the Penn Human Precision Pain Center (Penn HPPC) to elucidate molecular, cellular, epigenetic, and physiological profiles of human trigeminal ganglion (TG) sensory neurons at baseline and migraine conditions. The Penn HPPC will be composed of Penn and international investigators with multidisciplinary expertise. The PI, two MPIs, and two co-Is are currently collaborating on a single-soma deep RNA-seq of human dorsal root ganglion (DRG) neuron project, which form a strong foundation for this application. Specifically, the Penn HPPC will contain three cores and perform three projects. Among them, the data core will be the sole entity for storage, processing, and distribution of all data from the HPPC projects, which will be led Dr. Li, an expert in single-cell and spatial transcriptomics data analysis. The data core will provide professional expertise in biosta- tistics, bioinformatics, and computing to all three projects and investigators in the Penn HPPC Program. The data core will provide biostatistics design and analysis for all studies across the Program, including formulation of testable hypotheses, estimation of sample size and power, performance and interpretation of data analyses, and graphical display and interpretation of results. In addition, the core will provide bioinformatics expertise and analysis for the single-cell RNA-Seq (scRNA-seq) and spatial transcriptomics profiling experiments in Project 1 and single-cell multi-omics profiling experiments in Project 2. This support will include data quality checks, read mapping and normalization, removal of batch effects, clustering and cell type annotation for scRNA-seq, detec- tion of spatial domains and spatially variable genes and cell type deconvolution for spatial transcriptomics data, and integrative analysis of single-nucleus multi-omics data. The data core will perform single-cell and spatial data and single-nucleus multi-omics analysis using the latest methods. The data core will also make extensive use of modern methods of statistical computing and reproducible research tools. This capability will foster the sharing of analysis codes and results, the rapid deployment of novel analysis tools, and effective investigator access to program-wide data and knowledge management platforms for cross-project research discovery. Fi- nally, the data core will interact and work with U24 HEAL data centers for data storage, transfer, sharing, and integration. In summary, the Data Core is a vital component of each Project, which will facilitate novel discoveries of human pain biology proposed by Penn HPPC and the overarching goal of the NIH HEAL Initiative PRECISION Human Pain network.

偏头痛是最常见的原发性头痛疾病之一，影响着四分之一的美国家庭。这个综合体神经系统疾病部分是由三叉神经躯体感觉的改变介导的，表现为头/fa- 关节疼痛和/或三叉神经异常性疼痛。偏头痛的有效治疗方法仍然有限，而且我们对偏头痛的了解人类三叉神经系统的基线和偏头痛状况很少。回应 RFA-NS-22-018，治愈倡议：人类疼痛相关基因和细胞的发现和功能评估，我们建议成立宾夕法尼亚州人类精准疼痛中心 (Penn HPPC)，以阐明分子、细胞、表观遗传和人类三叉神经节 (TG) 感觉神经元在基线和偏头痛条件下的生理特征。宾夕法尼亚大学 HPPC 将由宾夕法尼亚大学和具有多学科专业知识的国际研究人员组成。这 PI、两个 MPI 和两个 co-Is 目前正在合作开展人类背根的单体细胞深层 RNA 测序神经节（DRG）神经元项目，为该应用奠定了坚实的基础。具体来说，宾夕法尼亚州 HPPC 将包含三个核心并执行三个项目。其中，数据核心将是唯一实体 HPPC 项目的所有数据的存储、处理和分发，将由 HPPC 项目专家李博士领导。单细胞和空间转录组数据分析。数据核心将提供生物稳态方面的专业知识向宾夕法尼亚大学 HPPC 计划的所有三个项目和研究人员提供统计学、生物信息学和计算方面的知识。这数据核心将为整个计划的所有研究提供生物统计学设计和分析，包括配方可检验的假设、样本量和功效的估计、数据分析的性能和解释，以及结果的图形显示和解释。此外，该核心还将提供生物信息学专业知识和项目1中单细胞RNA-Seq (scRNA-seq)和空间转录组学分析实验的分析以及项目 2 中的单细胞多组学分析实验。这种支持将包括数据质量检查、阅读作图和归一化、消除批次效应、scRNA-seq 的聚类和细胞类型注释、检测空间域和空间可变基因以及空间转录组数据的细胞类型反卷积，单核多组学数据的综合分析。数据核心将执行单细胞和空间使用最新方法进行数据和单核多组学分析。数据核心也将广泛使用现代统计计算方法和可重复的研究工具。这种能力将促进共享分析代码和结果、快速部署新颖的分析工具以及有效的研究者访问项目范围内的数据和知识管理平台以进行跨项目研究发现。菲- 最终，数据核心将与U24 HEAL数据中心进行交互和协作，进行数据存储、传输、共享和一体化。总之，数据核心是每个项目的重要组成部分，它将促进新的发现 Penn HPPC 提出的人类疼痛生物学研究和 NIH HEAL Initiative PRECISION 的总体目标人类疼痛网络。