Functional Networks in Diabetes-Progression by Comparison of Gene Expression in Three Tissues of Goto-Kakizaki Rats

Yidan      Sun; Xiao      Han; Shigeru      Saito; Katsuhisa      Horimoto; Huarong      Zhou

Abstract

The expression of genes in three tissue types, adipose, liver and muscle, from normal (Wistar-Kyoto) and diabetic (Goto-Kakizaki) rats, was analyzed to gain insight into the potential functional relationships between these tissues in diabetes progression. For this purpose, the gene expression signatures during different periods of diabetes progression were first obtained, and were characterized by the biological functions. The significant functions for the three tissues were then clustered into 10 groups, according to the constituent expression profiles in the corresponding gene sets. Finally, the relationships between the 10 functional groups were inferred by a statistical network analysis method. The numbers of genes in the expression signatures were similar in the three tissues for the three periods, but the numbers of significant biological functions showed a wider variety for the three tissues. One of the remarkable features is that the functions of liver and muscle commonly detected in the three periods were found in those of adipose at the early stage. The following network analyses revealed a sketch of the functional relationships between the three tissues. The relationships within the three tissues were not similar, but those between them shared functional interfaces, in which adipose at an early stage and muscle during all periods transmit functional information, and liver at the late stage receives it, in diabetes progression. Thus, the present approach for functional network estimation may provide insights about the macroscopic relationships in diabetes progression, and especially the initiator role of adipose.

Keywords: Diabetes progression, functional network, gene expression, Goto-Kakizaki rat, network inference, tissue relationship, Clustering Analysis, REACTOME_DIABETES_PATHWAYS, KEGG_ALZHEIMERS_DISEASE, macroscopic sketch