The merged networks for each dataset clustered around several central genes (Fig. 2, Fig. 3 and Fig. 4). To facilitate an objective comparison between networks and to gain further insights, we ranked the central genes according to the total number of connections linked to each one of them – the more the number selleck kinase inhibitor of connections, the higher the rank. The top 15 central genes and their directly linked focus genes are shown in Table 8. This analysis

revealed that seven central genes were common to all 3 ages, including transcription factors, hepatic nuclear factor 4, alpha (Hnf4a) and transformation related protein 53 (Trp53); anti-apoptotic factor, BCL2-like 1 (Bcl2l1); cytokines, interferon gamma (Ifng), interleukin 4 (Il4) and interleukin 15 (IL15); and the pro-inflammatory 3-Methyladenine research buy factor, prostaglandin E2. The pro-inflammatory cytokine, interleukin 6 (Il6) was common to ages 2 and 4 weeks. Other genes were unique to the respective age groups, e.g. to 2 weeks: transcription factors, myelocytomatosis oncogene (Myc), Jun oncogene (Jun), and amyloid beta (A4) precursor protein (App);

to 3 weeks: the pro-inflammatory cytokine, tumor necrosis factor (Tnf), the anti-inflammatory cytokine, Tgfb1 (transforming growth factor, beta 1), and cell signaling molecules NFκB, ERK, p38MAPK, and insulin-like growth factor 1 (Igf1); and to 4 weeks: cytokines, interferon alpha and IL12 (interleukin

12), the transcription factor signal transducer and activator of transcription 4 (Stat4), and Rous sarcoma oncogene (Src). Interestingly, the central genes Bcl2l1 and Src are also located within Idd13. The Protein tyrosine phosphatase biological processes associated with the central genes that were common to all 3 ages included apoptosis/cellular proliferation, Th1–Th2 balance, cytokine signaling, and inflammation. Those associated with the age-specific central genes included apoptosis/cell proliferation (at 2 weeks), cell signaling/cellular activation and inflammation (at 3 weeks), and innate immunity/link to adaptive immune response (at 4 weeks). Similar to the promoter analysis, each of the common central genes was connected to a different set of focus genes at the various ages, consisting of both age-common and age-specific genes, again suggesting a dynamic coordinated regulation of the molecular processes over time. These data suggest that abnormalities in apoptosis/cellular proliferation predominate at 2 weeks of age, while those in cell signaling/cellular activation and inflammation predominate at 3 weeks of age. Abnormalities in the innate immune response and its link to adaptive immunity predominate at 4 weeks of age.