Data Core

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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.