Molecular Precision Nephrology Core

分子精准肾病学核心

• 批准号: 10529734
• 负责人: KATALIN SUSZTAK
• 金额: $ 13.08万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10529734
• 关键词: APOL1 gene; Acute; Address; Atlases; Basophils; Biochemical; Bioinformatics; Biopsy Specimen; Cell Communication; Cell Lineage; Cell Nucleus; Cells; Child; Childhood; Chromatin; Clinical; Clinical Data; Clinical Research; Clinical Trials; Communication; Communities; Complement; Data; Data Set; Databases; Descriptor; Development; Diagnostic Procedure; Disease; Fostering; Freezing; Future; Gene Expression; Gene Expression Regulation; Generations; Genes; Genetic; Genotype; Goals; Heterogeneity; Histologic; Human; Informatics; Kidney; Kidney Diseases; Maps; Measurement; Methods; Molecular; Monitor; Multiomic Data; Mus; Nephrology; Nuclear; Nucleotides; Pathway interactions; Pediatrics; Pharmacology; Phase; Population Heterogeneity; Process; Prognosis; Proteins; Proteome; RNA; Recording of previous events; Research; Resolution; Resources; Role; Sampling; Small Nuclear RNA; Standardization; Therapeutic; Tissue Banks; Tissue Embedding; Tissue Sample; Tissues; Variant; analytical method; base; cell type; computerized tools; data acquisition; demographics; epigenome; ethnic diversity; genome-wide; high risk; human disease; improved; kidney biopsy; kidney cell; kidney fibrosis; multimodality; multiple omics; nephrogenesis; novel; personalized diagnostics; phenotypic data; reconstruction; repaired; sensor; single cell analysis; single-cell RNA sequencing; spatial integration; therapeutic development; therapeutic target; tool; transcriptome sequencing; treatment response; web interface

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.

分子精度肾脏病核心摘要 PCEN的分子精度肾脏科（MPN）核心的目标是促进 鉴定新目标并扩大肾脏疾病儿童的治疗选择。 当前可用的肾脏疾病的临床，生化和组织学描述是 不足，因为他们预测预后和治疗反应不足。精确的革命 分子测量正在进行中。新颖的精确诊断方法可以准确 监测全基因组基因表达，调节，功能，细胞病史和细胞 肾脏活检样品中的相互作用，可以突出可定位的变化。新颖的精度 由于定义的治疗靶标的缺乏，诊断方法在儿科至关重要， 肾脏疾病原因的异质性，以及进行大型临床试验的障碍。 分子的临床和研究实施有几个关键障碍 小儿肾脏科学上的精密工具：1，缺乏可用参考（正常健康）组织 样品2，没有高质量的小儿肾样品均匀加工核心3， 当前使用的单细胞分析方法的非线性，生成不可转让的 数据集之间的信息和需要单一的大量大量努力4，短缺 专门的生物信息学努力为儿科肾脏地图集而产生。 MPN核心将 解决这些障碍，并将引入小儿肾脏疾病研究的新阶段。 具体而言，MPN核心将： 创建斩波资源：切碎的肾脏纸巾库，包含新鲜，冷冻，固定的 来自健康和患病的小儿肾样品的嵌入式组织样品来自种族 多样化的人群以及一个包含人口统计，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研究基础的组织样品。 提供统一的综合多模式小儿肾细胞地图集，并促进其在 参与社区。这将使用新的计算工具来实现 引起疾病的基因，细胞类型和机制，重点是细胞类型注释， 细胞谱系和细胞电池通信的重建以及空间多摩变的整合 单细胞信息，临床，人口统计学和遗传数据。