Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation
Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation
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DOI：
10.1038/ng1305
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发表时间：
2004-03-01
期刊：
影响因子：
30.8
通讯作者：
Golub, TR
中科院分区：
文献类型：
--
作者：
Stegmaier, K;Ross, KN;Golub, TR
化学基因组学涉及产生大量小分子并利用它们来调节细胞状态。尽管最近在结构多样的化合物的系统合成方面取得了进展，但它们在细胞电路筛选中的使用仍然是一个临时过程(1-4)。在这里，我们概述了一种称为基于基因表达的高通量筛选（GE-HTS）的通用、有效的方法，其中基因表达特征被用作细胞状态的替代，并且我们描述了其在特定环境中的应用：鉴定诱导急性髓系白血病细胞分化的化合物。在筛选 1,739 种化合物时，我们鉴定了 8 种能够可靠地诱导分化特征，此外，还产生了真正分化的功能证据。结果表明 GE-HTS 可能是一种强大的通用化学筛选方法。
Chemical genomics involves generating large collections of small molecules and using them to modulate cellular states. Despite recent progress in the systematic synthesis of structurally diverse compounds, their use in screens of cellular circuitry is still an ad hoc process(1-4). Here, we outline a general, efficient approach called gene expression based high-throughput screening (GE-HTS) in which a gene expression signature is used as a surrogate for cellular states, and we describe its application in a particular setting: the identification of compounds that induce the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature and, furthermore, yielded functional evidence of bona fide differentiation. The results indicate that GE-HTS may be a powerful, general approach for chemical screening.