FIGURE 2.

Human target validation and prioritization. After generation of CKD target lists, additional disease-relevant evidence is added to generate testable hypotheses and to prioritize the candidates. Tissue-specific expression enrichment and expression modulation in disease versus healthy states help to ascertain the role of targets in CKD. Correlation of targets with renal functional biomarkers and parameters is ascertained and target expression across CKD stages or etiologies is explored to add confidence around disease relevance. Prediction of target kidney cell type is useful for guiding downstream in vitro validation and assay selection. Pathway and network analyses can provide additional biological context for dysregulated cellular mechanisms and help infer potential mechanisms of action. The accumulated evidence supporting human target validation and mechanism of action results in a set of prioritized candidates for further experimental validation. CKD, chronic kidney disease; DN, diabetic nephropathy; eGFR, estimated glomerular filtration rate; eQTL, expression quantitative trait loci; FSGS, focal segmental glomerulosclerosis; HT, hypertensive nephropathy; IgA, immunoglobulin A nephropathy; MCD, minimal change disease; MGN, membranous glomerulonephritis; RPGN, rapid progressive glomerulonephritis; SLE, systemic lupus erythematosus.