Molecular Precision Nephrology Core

分子精密肾脏学核心总结 PCEN的分子精密肾病学（MPN）核心的目标是促进 确定新的靶点并扩大肾病儿童的治疗选择。 目前可用的肾脏疾病的临床、生化和组织学描述是 这是不够的，因为它们预测预后和治疗反应很差。精度革命 分子测量正在进行中。新的精确诊断方法可以准确地 监测全基因组基因表达、调控、功能、细胞历史和细胞 肾活检样本中的相互作用，可以突出目标变化。新型精准 诊断方法在儿科中由于缺乏确定的治疗靶点而至关重要， 肾脏疾病病因的异质性以及开展大型临床试验的障碍。 分子生物学的临床和研究实施存在几个关键障碍， 儿科肾脏学中的精密工具：1，缺乏可用的参考（正常健康）组织 样品2，缺乏用于儿科肾脏样品3的高质量均匀处理芯， 目前使用的单细胞分析方法的非线性，产生不可转移的 数据集之间的信息，并需要单一的大型地图集的努力4，短缺 专门的生物信息学工作，用于生成儿科肾脏图谱。MPN核心将 解决这些障碍，并将迎来儿科肾脏疾病研究的新阶段。 具体而言，MPN核心将： 创建CHOP-KID资源：CHOP肾脏组织库，包含新鲜，冷冻，固定 来自健康和患病儿童肾脏样本的包埋组织样本， 不同的人群和相关的去识别数据库，其中包含人口统计学、临床和 组织学注释。 生成参考单细胞表达、表观基因组、空间表达和蛋白质组图谱 为肾脏发育和成熟，并作为核心处理和比较疾病 为PCEN研究基地提供组织样本。 提供协调的综合多模态儿科肾细胞图谱，并促进其在 参与社区。这将通过使用新的计算工具来识别 致病基因，细胞类型和机制，专注于细胞类型注释， 细胞谱系和细胞间通讯的重建，以及空间多组学的整合 单细胞信息、临床、人口统计学和遗传学数据。

MOLECULAR PRECISION NEPHROLOGY CORE SUMMARY The goal of the Molecular Precision Nephrology (MPN) Core of the PCEN is to facilitate identification of novel targets and expand therapeutic options for children with kidney disease. The currently available clinical, biochemical and histological descriptors for kidney disease are insufficient, as they poorly predict prognosis and therapeutic response. A revolution in precision molecular measurements is underway. Novel precision diagnostic methods can accurately monitor genome-wide gene expression, regulation, function, cellular history and cellular interactions in kidney biopsy samples and can highlight targetable changes. Novel precision diagnostic methods are critical in pediatrics due to the paucity of defined therapeutic targets, heterogeneity of causes of kidney diseases, and barriers to conducting large clinical trials. There are several critical barriers to the clinical and research implementation of molecular precision tools in pediatric nephrology: 1, the lack of available reference (normal healthy) tissue samples 2, absence of a high quality uniformly processing core for pediatric kidney samples 3, non-linearity of currently used single cell analytical methods, generating non-transferrable information between datasets and necessitating single large atlasing efforts 4, shortage of dedicated bioinformatics effort for the generation of a pediatric kidney atlas. The MPN Core will address these barriers and will usher in a new phase of pediatric kidney disease research. Specifically, the MPN Core will: Create the CHOP-KID resource: the CHOP kidney tissue bank, containing fresh, frozen, fixed embedded tissue samples from healthy and diseased pediatric kidney samples from an ethnically diverse population and an associated de-identified database containing demographic, clinical and histological annotation. Generate reference single cell expression, epigenome, spatial expression and proteome maps for kidney development and maturation and serve as a core to process and compare disease tissue samples for the PCEN research base. Deliver a harmonized integrated multi-modal pediatric kidney cell atlas and foster its use in the engaged community. This will be accomplished using new computational tools for identification of disease-causing genes, cell types and mechanisms, focusing on cell type annotation, reconstruction of cell lineages and cell-cell communications, and integration of spatial multi-omics single cell information, clinical, demographic, and genetic data.