Abstract
The Kidney Precision Medicine Project (KPMP) plans to construct a spatially specified tissue atlas of the human kidney at a cellular resolution with near comprehensive molecular details. The atlas will have maps of healthy, acute kidney injury and chronic kidney disease tissues. To construct such maps, we integrate different data sets that profile mRNAs, proteins and metabolites collected by five KPMP Tissue Interrogation Sites. Here, we describe a set of hierarchical analytical methods to process, combine, and harmonize single-cell, single-nucleus and subsegmental laser microdissection (LMD) transcriptomics with LMD and near single-cell proteomics, 3-D nondestructive and immunofluorescence-based Codex imaging and spatial metabolomics datasets. We use nephrectomy, healthy living donor and surveillance transplant biopsy tissues to create a harmonized reference tissue map. Our results demonstrate that different assays produce reliable and coherent identification of cell types and tissue subsegments. They further show that the molecular profiles and pathways are partially overlapping yet complementary for cell type-specific and subsegmental physiological processes. Focusing on the proximal tubules, we find that our integrated systems biologybased analyses identify different subtypes of tubular cells with potential for different levels of lipid oxidation and energy generation. Integration of our omics data with pathways from the literature, enables us to construct predictive computational models to develop a smart kidney atlas. These integrated models can describe physiological capabilities of the tissues based on the underlying cell types and pathways in health and disease.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
