Computational Systems Bioinformatics and Bioimaging for Pathway Analysis and Drug Screening.
Computational Systems Bioinformatics and Bioimaging for Pathway Analysis and Drug Screening.
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用于途径分析和药物筛选的计算系统生物信息学和生物成像。
DOI：
10.1109/jproc.2008.925440
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Wong,StephenTC
中科院分区：
文献类型：
--
作者：
Zhou,Xiaobo;Wong,StephenTC
当今药物开发的前提是疾病的机制高度依赖于潜在的信号传导和细胞途径。这些途径通常由物理相互作用的基因、蛋白质或由代谢中间体、离子和其他小溶质协调的生物化学活动的复合物组成，并且用基因组学、蛋白质组学和代谢组学中的分子生物学方法进行研究。然而，最近制药业收入的下降表明，单靠这种方法可能不足以创造成功的新药。我们的观察是，将基因组学、蛋白质组学和代谢组学的方法与生物成像技术相结合，将系统地提供强大的手段来解码或更好地理解导致疾病的分子相互作用和途径，并可能产生新的见解和药物靶点的适应症。前一种方法提供基因、蛋白质和代谢物的谱，而后一种技术产生与分子谱和相互作用相关的客观、定量表型。在本文中，我们描述了途径重建和目标验证的基础上提出的系统生物学方法，并显示选定的应用程序的路径分析和药物筛选的例子。
The premise of today's drug development is that the mechanism of a disease is highly dependent upon underlying signaling and cellular pathways. Such pathways are often composed of complexes of physically interacting genes, proteins, or biochemical activities coordinated by metabolic intermediates, ions, and other small solutes and are investigated with molecular biology approaches in genomics, proteomics, and metabonomics. Nevertheless, the recent declines in the pharmaceutical industry's revenues indicate such approaches alone may not be adequate in creating successful new drugs. Our observation is that combining methods of genomics, proteomics, and metabonomics with techniques of bioimaging will systematically provide powerful means to decode or better understand molecular interactions and pathways that lead to disease and potentially generate new insights and indications for drug targets. The former methods provide the profiles of genes, proteins, and metabolites, whereas the latter techniques generate objective, quantitative phenotypes correlating to the molecular profiles and interactions. In this paper, we describe pathway reconstruction and target validation based on the proposed systems biologic approach and show selected application examples for pathway analysis and drug screening.