Molecular Precision Nephrology Core

分子精密肾病核心综述 PCEN的分子精密肾脏学(MPN)核心的目标是促进 确定新的靶点，扩大肾脏疾病儿童的治疗选择。 目前可用的肾脏疾病的临床、生化和组织学描述为 不足，因为它们很难预测预后和治疗反应。精确度的革命 分子测量正在进行中。新的精确诊断方法可以准确地 监测全基因组的基因表达、调节、功能、细胞历史和细胞 在肾脏活检样本中的相互作用，并可以突出目标变化。新奇的精度 由于缺乏明确的治疗目标，诊断方法在儿科中至关重要， 肾脏疾病病因的异质性，以及进行大型临床试验的障碍。 分子生物学的临床和研究实施有几个关键障碍 儿科肾脏病的精密工具：1、缺乏可用的参照物(正常健康)组织 样品2，缺乏高质量的统一处理的儿科肾脏样品3， 当前使用的单细胞分析方法的非线性，产生不可转移 数据集之间的信息和需要的单一大型地图集工作4，短缺 致力于生物信息学工作，以生成一份儿童肾脏图谱。MPN核心将 解决这些障碍，将开启儿科肾脏疾病研究的新阶段。 具体而言，MPN核心将： 打造斩肾资源：斩肾组织库，包含新鲜、冷冻、固定 来自一个种族的健康和患病儿童肾脏样本的包埋组织样本 多样化的人口和相关的未识别数据库，其中包含人口、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 用于肾脏发育和成熟，并作为处理和比较疾病的核心 PCEN研究基地的组织样本。 提供协调统一的多模式儿童肾脏细胞图谱，并促进其在 积极参与的社区。这将使用新的身份识别计算工具来实现 致病基因、细胞类型和致病机制，重点是细胞类型注释， 重建细胞谱系和细胞间通讯，整合空间多组学 单细胞信息、临床、人口统计学和基因数据。

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.