The systems biology of human complex diseases is still in its infancy due to the intricate pathological mechanisms. New methods or strategies should be developed to elucidate the development of complex diseases, such as cancer and cardiovascular disease. In this study, comparative systems biology was introduced based on the integrated high-throughput data and computational methods. Animal models have been extensively used in the study of cardiovascular disease (CVD) and provided important insights into disease pathogenesis and drug development. However, the level of conservation of gene expression patterns of the orthologous genes between human and animal models has been unclear. To address the issue, we compared gene expression of orthologous genes between human and four models (rhesus, rat, mouse and dog) based on 42 normal heart samples with high quality gene expression data. The results shows although the global expression profiles between animal models and human orthologous genes are highly preserved, some pathways such as proteasome, aminoacyl-tRNA biosynthesis and GST (Glycine, Serine and Threonine) metabolism were functionally divergent between models and human. The co-expression network based on intra- and inter-species variation indicates that the differentially expressed genes evolved as modules rather than independently. Besides, we reconstructed and analyzed metabolic networks in six anatomically and functionally distinct regions of the Alzheimer’s disease brain. The results show that the six metabolic networks contain region-specifically expressed genes which provide specific microenvironment for different brain regions. Using the models, we predicted a set of 119 biomarkers whose concentrations are predicted to be either elevated or reduced because of 55 possible dysfunctional enzymes. The comparison of mouse and human metabolic models reveals that the expression states between human and mouse are of apparent differences, mainly in the expression states of lipid metabolism-related genes. Comparative systems biology may provide valuable information for the development of animal models of human complex diseases and personal medicine.
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