Target deconvolution techniques in modern phenotypic profiling.
Target deconvolution techniques in modern phenotypic profiling.
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DOI：
10.1016/j.cbpa.2012.12.022
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发表时间：
2013-02
影响因子：
7.8
通讯作者：
Bogyo, Matthew
中科院分区：
文献类型：
--
作者：
Lee, Jiyoun;Bogyo, Matthew
在过去的十年中，在经典的表型筛选中使用不同的化合物文库来鉴定给定过程的调节剂的情况迅速增长。识别活性命中的分子靶标的后续过程，也称为“靶标去卷积”，是理解化合物作用机制和使用所识别的命中作为进一步剖析给定生物过程的工具的必要步骤。“组学”技术的最新进展，加上计算机模拟方法和全基因组测序成本的降低，极大地改善了目标去卷积的工作流程，并促进了“现代”表型分析的复兴。在本文中，我们将概述如何在目标识别和验证的困难过程中使用新技术和旧技术，并讨论表型筛选中仍然存在的一些持续挑战。
The past decade has seen rapid growth in the use of diverse compound libraries in classical phenotypic screens to identify modulators of a given process. The subsequent process of identifying the molecular targets of active hits, also called ‘target deconvolution’, is an essential step for understanding compound mechanism of action and for using the identified hits as tools for further dissection of a given biological process. Recent advances in ‘omics’ technologies, coupled with in silico approaches and the reduced cost of whole genome sequencing, have greatly improved the workflow of target deconvolution and have contributed to a renaissance of ‘modern’ phenotypic profiling. In this review, we will outline how both new and old techniques are being used in the difficult process of target identification and validation as well as discuss some of the ongoing challenges remaining for phenotypic screening.
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