Data Core

偏头痛是最常见的原发性头痛疾病之一，影响四分之一的美国家庭。这个复杂 神经障碍部分由三叉神经躯体感觉的改变介导，三叉神经躯体感觉的改变表现为头/发- 坐骨神经痛和/或三叉神经异常性疼痛。偏头痛的有效治疗方法仍然有限，我们对偏头痛的认识 人三叉神经系统在基线和偏头痛条件下是稀疏的。响应RFA-NS-22-018，HEAL 计划：人类疼痛相关基因和细胞的发现和功能评价，我们建议 成立宾州人类精确疼痛中心（Penn HPPC），以阐明分子，细胞，表观遗传， 在基线和偏头痛条件下的人三叉神经节（TG）感觉神经元的生理概况。 Penn HPPC将由具有多学科专业知识的Penn和国际研究人员组成。的 PI，两个MPI和两个co-I目前正在合作进行人类背根的单细胞体深层RNA测序 神经节（DRG）神经元项目，这为该应用奠定了坚实的基础。具体来说，Penn HPPC 将包含三个核心并执行三个项目。其中，数据核心将是唯一的实体， 存储，处理和分发来自HPPC项目的所有数据，这将由李博士领导，他是一位专家， 单细胞和空间转录组学数据分析。数据核心将提供生物统计方面的专业知识， 统计学，生物信息学和计算的所有三个项目和研究人员在宾夕法尼亚大学HPPC计划。的 数据核心将为整个项目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，核心将提供生物信息学专业知识， 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 和项目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 scRNA-seq的映射和标准化、批量效应的去除、聚类和细胞类型注释、检测 空间域和空间可变基因的分离以及空间转录组学数据的细胞类型去卷积， 和单核多组学数据的综合分析。数据核心将执行单像元和空间 数据和单核多组学分析使用最新的方法。数据核心还将使广泛的 使用现代统计计算方法和可重复的研究工具。这一能力将促进 共享分析代码和结果，快速部署新的分析工具，以及有效的调查员 访问全项目范围的数据和知识管理平台，以进行跨项目研究发现。菲- 最后，数据核心将与U24 HEAL数据中心进行交互和工作，以实现数据存储、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 由Penn HPPC提出的人类疼痛生物学和NIH HEAL Initiative PRECISION的总体目标 人类疼痛网络。

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.