The analysis of a time-course transcriptome profile by systems biology approaches reveals key molecular processes in acute kidney injury

Abstract

Background: Acute kidney injury is a common debilitating disease with no curative treatment. The recent development of big biological data is expected to expand our understanding of the disorder if appropriately analyzed to generate translational knowledge. We have here re-analyzed a time-course microarray data on mRNA expression of rat kidneys exposed to ischemia-reperfusion to identify key underlying biological processes. Materials and Methods: The dataset was quality controlled by principal component analysis and hierarchical clustering. Using limma R package, differentially expressed (DE) genes were detected which were then clustered according to their expression trajectories. The biological processes related to each cluster were harvested using gene ontology enrichment analysis. In addition, the interaction map of proteins encoded by the DE genes was constructed, and the functions related to network central genes were determined. Furthermore, signaling pathways related to the DE genes were harvested using pathway enrichment analysis. Results: We found 8139 DE genes that drive critical processes such as the control of blood circulation, reactive species metabolism, mitochondrial respiration, apoptosis, cell proliferation, as well as inflammatory and immunological reactions. The role of less recognized pathways such as olfactory signaling in acute kidney injury is also proposed that remains to be investigated in future studies. Conclusion: Using systems biology top-down approach, we have suggested novel potential genes and pathways to be intervened toward kidney regeneration.

Keywords

• acute kidney injury
• reperfusion injury
• systems biology