Figure 4 | Scientific Reports

Figure 4

From: Identification of pathological transcription in autosomal dominant polycystic kidney disease epithelia

Figure 4

Function-based mapping of CD178 identified ADPKD-related protein networks. (a) CD178 was used as input for STRING network analysis37. No annotations were available for 2610203C20Rik and 6330403L08Rik. Application of the k-means algorithm to CD178 revealed 3 distinct clusters: A with 10 proteins (A10); B with 8 proteins (B8); and C with 7 proteins (C7; total = ABC25). (b) and (c) to facilitate interpretation of the observed clusters, gene set enrichment analysis (GSEA) was applied to both CD178 and ABC25 (FDR < 0.05). ABC25 genes were subjected to an extended analysis, comprising hallmark gene sets, gene ontology (GO) analysis, transcription factor target analysis and evaluation of the Kyoto Encyclopedia of Genes and Genomes (KEGG)42,96,97,98. See Table S7 for full results. (d) To elucidate CD178 transcriptional regulation, ShinyGO and GeneSetDB meta-databases were queried (FDR < 0.05)41,42. This revealed a total of 17 CD178 genes regulated by 7 trancriptional factors (TF7). (e) 6 of 7 TF7 were shown to form a k-means based cluster. Also, ABC25 identified several regulatory cascades: 5 ABC25 genes (Cd34, Spp1, Cdh2, C3 and Mmp2) were linked to 6 of the TF7 (Ar, Esr1, Ets, Gli1, Rbpj, Tp53). Spp1 and Cdh2 were regulated by more than one TF7, whereas Ets2, Rbpj and Tp53 regulated more than one ABC25 gene.

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