Network clustering along diabetes progression in three tissues of Goto-Kakizaki rats

Xinrong Zhou, Katsuhisa Horimoto, Shigeru Saito, Luonan Chen, Huarong Zhou

Abstract: We investigated the macroscopic changes in the regulatory coordination of diabetes progression during three periods in three tissues, adipose, liver and muscle, of Goto-Kakizaki (GK) rats. For this purpose, we performed network clustering by the Newman algorithm for the regulatory networks inferred by a modified path consistency algorithm, and investigated the biological functions of each cluster by an enrichment analysis of the constituent genes. We then compared the network clusters characterized by biological functions with the diabetes progression of GK rats in each of the three tissues. The network structure, the number of clusters, and the number of clusters characterized by biological functions during the three periods showed similar patterns in the three tissues. In contrast, further scrutiny of the biological functions at coordinated clusters revealed characteristic differences between the three tissues along the diabetes progression. In particular, the hypothetical roles of each tissue emerged: adipose and liver function at the cellular and molecular levels at the early stage, respectively, and all three tissues are responsible for diabetes progression, under the control of various transcriptional regulators.