Biological complexity and drug discovery: a practical systems biology approach
Biological complexity and drug discovery: a practical systems biology approach
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DOI：
10.1049/ip-syb:20050036
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发表时间：
2005-12-01
期刊：
影响因子：
--
通讯作者：
Hytopoulos, E
中科院分区：
文献类型：
--
作者：
Berg, EL;Kunkel, EJ;Hytopoulos, E
药物在临床研究中失败的原因通常是缺乏疗效或意外的毒性。这些失败是由于对药物作用的理解不足，部分原因是我们依赖药物发现技术，而这些技术没有考虑到人类疾病生物学的复杂性。生物系统表现出复杂工程系统的许多特征，包括模块性、冗余性、鲁棒性和涌现性。解决这些问题有助于成功设计用于炎症药物发现的改进的生物测定技术。这种方法被称为生物多路复用活性分析（BioMAP），涉及从新型复杂的原代人类细胞为基础的测定系统产生的蛋白质数据集的统计分析。在这些系统中的化合物分析已经揭示，可以检测和区分数量惊人的生物学机制。这些分析相关的复杂系统的行为的特点进行了描述。
Drugs fail in clinical studies most often from lack of efficacy or unexpected toxicities. These failures result from an inadequate understanding of drug action and follow, in part, from our dependence on drug discovery technologies that do not take into account the complexity of human disease biology. Biological systems exhibit many features of complex engineering systems, including modularity, redundancy, robustness, and emergent properties. Addressing these features has contributed to the successful design of an improved biological assay technology for inflammation drug discovery. This approach, termed Biologically Multiplexed Activity Profiling (BioMAP), involves the statistical analysis of protein datasets generated from novel complex primary human cell-based assay systems. Compound profiling in these systems has revealed that a surprisingly large number of biological mechanisms can be detected and distinguished. Features of these assays relevant to the behaviour of complex systems are described.