An Integrative Informatics Approach to Identify Drug Targets and Therapies for Chronic Allograft Injury after Kidney Transplantation

We performed a meta-analysis of biopsy and peripheral blood samples from publicly available microarray datasets in GEO using a two-step meta-analysis method. Our in-house 22 microarray dataset is one of the datasets. We identified 85 immune-related genes that were associated with CAI. We then sought to discover novel therapeutic relationships between drug compounds and CAI through cMAP, a large-scale integration of public gene expression data for drugs and disease. We proposed that drugs that have a potentially therapeutic effect will be able to reverse the differential expression of the 85 CAI-specific gene set during drug exposure in a modeled cell line. We selected two drugs for in vivo and in vitro validations, kaempferol and esculetin, two plant-derived compounds that were ranked at the top of the 1,309 compounds. Biopsies obtained at 12 months post-transplantation from renal allograft recipients (n=22) were analyzed for gene expression by Affymetrix exon arrays.