Figure 1

Schematic representation of combinatorial approach identifying genes, molecular pathways and target miRNAs in ADPKD. mRNA expression profilings at E14.5 and E17.5 were analysed by limma package in Bioconductor R. Differentially expressed (DE) genes were obtained for comparisons- Mutant vs. WT at E14.5, at E17.5 and E14.5 vs E17.5 for mutants. Gene Ontology (GO) was used to compare the dominant biological processes in mutant and WT at each time point. Gene set enrichment analysis (GSEA) was performed to identify gene pathways associated with PKD progression and renal cyst growth; and to search for overrepresented TF promoter binding motifs among DE genes. Target miRNAs for DE genes at each comparison were predicted using TargetScan, miRanda, miRDB and microT and results were overlapped using Perl scripts. A subset of DE genes associated with PKD (as revealed from GO and GSEA analysis) and targeted by miRNAs (revealed by target prediction tools), was selected for verification by qPCR. miRNAs predicted to target DE genes by atleast two tools, were selected for verification by qPCR. Additionally, comparison of DE genes with other data sets on ADPKD were performed to derive set of pathways core to ADPKD.