Figure 3

Gene expression profile of Clr-f^−/− kidneys reveals progressive dysregulation in metabolism and stress response. (A) Schematic of RNA sequencing pipeline. (B) Interaction network of gene set enrichment analysis for biological processes differentially enriched in Clr-f^−/− mice compared to WT at 7, 13, and 24 weeks. Blue nodes represent gene sets enriched with downregulated transcripts (Log₂ FC < 0), and red nodes represent gene sets enriched with upregulated transcripts (Log₂ FC > 0), according to the Normalized Enrichment Score (NES) color scale shown. Interaction map was constructed using Cytoscape V3.7.1 (C) Heatmaps represent Clr-f^−/− DEGs that belong to four dynamic patterns of expression: DEGs that increase with age, decrease with age, and DEGs that transiently increase or decrease at 13 weeks of age. Three sub-clusters of genes identified within each dynamic expression pattern represent three distinct variations in expression dynamics within the four aforementioned groups. The mean Log₂FC of DEG sub-clusters within each dynamic pattern is plotted against time with lines of best fit shown (using least-squares second-order polynomial). Gene ontology categorization of GO:Biological Processes/GO:Molecular Function for genes belonging to the three sub-clusters of each dynamic pattern is indicated by red squares, with color intensity according to fold enrichment. Pathways enriched from KEGG pathways are shown for all genes belonging to each of the four dynamic patterns of expression. Heat map was constructed using Morpheus (https://software.broadinstitute.org/morpheus).