Ji et al. BMC Genomics 2012, 13:441 http://www.biomedcentral.com/1471-2164/13/441 Page 6 of 16 (See figure on previous page.) Figure 2 Cluster analysis of differentially expressed genes. The 2016 genes differentially expressed in one or both treatment groups vs. fed controls were subjected to hierarchical clustering to visualize similarities and differences between treatment groups. (A). Hierarchical cluster analysis of the 2016 genes (FDR adjusted p-value <0.05) that were differentially expressed between insulin-neutralized vs. fed and/or fasted vs. fed states. (B) Seven clusters (numbers) representing the most distinct effects of treatment were selected to further analyze expression profiles across treatments. Sample ID number on the X-axis corresponds to treatment group: sample 1–5, fasted; 6–10, insulin neutralized; 11–15,fed control. Y-axis represents relative gene expression value. Table 2 Gene ontology (GO) and KEGG annotation for representative clusters of differentially expressed genes Cluster 1, 3 and 4 (731 genes) Annotation GO GO term (Biological Process, level 6 or 7) or KEGG pathway name FDR p-value Positive regulation of protein metabolic process Negative regulation of cellular macromolecule biosynthetic process Triglyceride metabolic process Negative regulation of gene expression Proteolysis involved in cellular protein catabolic process 2 (557 genes) 6 (402 genes) 5 and 7 (250 genes) KEGG GO KEGG KEGG GO KEGG Negative regulation of kinase activity Regulation of transcription, DNA-dependent Protein phosphorylation Antigen receptor-mediated signaling pathway Regulation of phosphate metabolic process Regulation of kinase activity Regulation of I-kappaB kinase/NF-kappaB cascade Ubiquitin mediated proteolysis Sphingolipid metabolism PPAR signaling pathway Fatty acid metabolism Peroxisome Monosaccharide catabolic process DNA dependent DNA replication Hexose metabolic process Glucose metabolic process Regulation of cell shape DNA replication Nucleoside triphosphate metabolic Glycolysis / Gluconeogenesis Citrate cycle (TCA cycle) Steroid biosynthesis Glyoxylate and dicarboxylate metabolism Pyruvate metabolism Enzyme linked receptor protein signaling pathway Regulation of cellular protein metabolic process Negative regulation of macromolecule metabolic process Transmembrane receptor protein serine/threonine kinase signaling pathway Negative regulation of protein metabolic process Positive regulation of cellular metabolic process PPAR signaling pathway Glycerolipid metabolism MAPK signaling pathway 6.0 E-3 7.3 E-3 1.0 E-2 1.0 E-2 1.0 E-2 1.5 E-2 2.1 E-2 3.3 E-2 3.3 E-2 3.4 E-2 3.4 E-2 3.5 E-2 1.0 E-2 1.8 E-2 2.4 E-2 4.6 E-2 5.0 E-2 2.5 E-2 3.6 E-3 1.1 E-2 1.4 E-2 1.5 E-2 1.5 E-2 2.3 E-2 4.9 E-4 8.9 E-4 4.4 E-3 1.2 E-2 3.3 E-2 9.7 E-3 3.1 E-2 3.5 E-2 3.6 E-2 3.7 E-2 4.4 E-2 1.0 E-4 1.8 E-2 4.6 E-2