Chanda Sumit K, Caldwell Jeremy S
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Drug Discov Today. 2003 Feb 15;8(4):168-74. doi: 10.1016/s1359-6446(02)02595-3.
The genomic era has brought with it a basic change in experimentation, enabling researchers to look more comprehensively at biological systems. The sequencing of the human genome coupled with advances in automation and parallelization technologies have afforded a fundamental transformation in the drug target discovery paradigm, towards systematic whole genome and proteome analyses. In conjunction with novel proteomic techniques, genome-wide annotation of function in cellular models is possible. Overlaying data derived from whole genome sequence, expression and functional analysis will facilitate the identification of causal genes in disease and significantly streamline the target validation process. Moreover, several parallel technological advances in small molecule screening have resulted in the development of expeditious and powerful platforms for elucidating inhibitors of protein or pathway function. Conversely, high-throughput and automated systems are currently being used to identify targets of orphan small molecules. The consolidation of these emerging functional genomics and drug discovery technologies promises to reap the fruits of the genomic revolution.
基因组时代给实验带来了根本性的变化,使研究人员能够更全面地审视生物系统。人类基因组测序以及自动化和并行化技术的进步,为药物靶点发现模式带来了根本性的转变,朝着系统的全基因组和蛋白质组分析发展。结合新颖的蛋白质组学技术,对细胞模型中的功能进行全基因组注释成为可能。叠加来自全基因组序列、表达和功能分析的数据,将有助于识别疾病中的致病基因,并显著简化靶点验证过程。此外,小分子筛选方面的几项并行技术进步,促成了用于阐明蛋白质或信号通路功能抑制剂的快速且强大平台的开发。相反,高通量和自动化系统目前正用于识别孤儿小分子的靶点。这些新兴的功能基因组学和药物发现技术的整合有望收获基因组革命的成果。