Moradzadeh Kobra, Gheisari Yousof
Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.
Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Res Med Sci. 2019 Jan 31;24:3. doi: 10.4103/jrms.JRMS_690_18. eCollection 2019.
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.
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.
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.
Using systems biology top-down approach, we have suggested novel potential genes and pathways to be intervened toward kidney regeneration.
急性肾损伤是一种常见的使人衰弱的疾病，尚无治愈性治疗方法。如果对大生物数据进行适当分析以产生转化知识，有望扩展我们对该疾病的理解。我们在此重新分析了关于缺血再灌注大鼠肾脏mRNA表达的时间进程微阵列数据，以确定潜在的关键生物学过程。
通过主成分分析和层次聚类对数据集进行质量控制。使用limma R包检测差异表达（DE）基因，然后根据其表达轨迹进行聚类。使用基因本体富集分析收集与每个聚类相关的生物学过程。此外，构建了DE基因编码蛋白质的相互作用图谱，并确定了与网络中心基因相关的功能。此外，使用通路富集分析收集与DE基因相关的信号通路。
我们发现8139个DE基因驱动着诸如血液循环控制、活性物质代谢、线粒体呼吸、细胞凋亡、细胞增殖以及炎症和免疫反应等关键过程。还提出了嗅觉信号等较少被认识的通路在急性肾损伤中的作用，有待未来研究进一步探究。
采用系统生物学自上而下的方法，我们提出了有待干预以促进肾脏再生的新的潜在基因和通路。
