Cisek Katryna, Krochmal Magdalena, Klein Julie, Mischak Harald
Mosaiques Diagnostics GmbH, Hannover, Germany.
Biotechnology Division, Biomedical Research Foundation Academy of Athens, Athens, Greece.
Nephrol Dial Transplant. 2016 Dec;31(12):2003-2011. doi: 10.1093/ndt/gfv364. Epub 2015 Oct 20.
The quest for the ideal therapeutic target in chronic kidney disease (CKD) has been riddled with many obstacles stemming from the molecular complexity of the disease and its co-morbidities. Recent advances in omics technologies and the resulting amount of available data encompassing genomics, proteomics, peptidomics, transcriptomics and metabolomics has created an opportunity for integrating omics datasets to build a comprehensive and dynamic model of the molecular changes in CKD for the purpose of biomarker and drug discovery. This article reviews relevant concepts in omics data integration using systems biology, a mathematical modelling method that globally describes a biological system on the basis of its modules and the functional connections that govern their behaviour. The review describes key databases and bioinformatics tools, as well as the challenges and limitations of the current state of the art, along with practical application to CKD therapeutic target discovery. Moreover, it describes how systems biology and visualization tools can be used to generate clinically relevant molecular models with the capability to identify specific disease pathways, recognize key events in disease development and track disease progression.
对慢性肾脏病(CKD)理想治疗靶点的探索一直充满诸多障碍,这些障碍源于该疾病及其合并症的分子复杂性。组学技术的最新进展以及由此产生的涵盖基因组学、蛋白质组学、肽组学、转录组学和代谢组学的大量可用数据,为整合组学数据集以构建CKD分子变化的全面动态模型创造了机会,目的是发现生物标志物和药物。本文回顾了使用系统生物学进行组学数据整合的相关概念,系统生物学是一种数学建模方法,基于生物系统的模块及其行为的功能连接对其进行全局描述。该综述描述了关键数据库和生物信息学工具,以及当前技术水平的挑战和局限性,以及在CKD治疗靶点发现中的实际应用。此外,它还描述了如何使用系统生物学和可视化工具来生成具有识别特定疾病途径、识别疾病发展中的关键事件和跟踪疾病进展能力的临床相关分子模型。