Molecular Precision Nephrology Core

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.