Gibbons Francis D, Proft Markus, Struhl Kevin, Roth Frederick P
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Longwood Avenue, Boston, MA 02115, USA.
Genome Biol. 2005;6(11):R96. doi: 10.1186/gb-2005-6-11-r96. Epub 2005 Nov 1.
Chromatin immunoprecipitation combined with microarray technology (Chip2) allows genome-wide determination of protein-DNA binding sites. The current standard method for analyzing Chip2 data requires additional control experiments that are subject to systematic error. We developed methods to assess significance using variance stabilization, learning error-model parameters without external control experiments. The method was validated experimentally, shows greater sensitivity than the current standard method, and incorporates false-discovery rate analysis. The corresponding software ('Chipper') is freely available. The method described here should help reveal an organism's transcription-regulatory 'wiring diagram'.
染色质免疫沉淀结合微阵列技术(Chip2)可实现全基因组范围内蛋白质-DNA结合位点的测定。目前分析Chip2数据的标准方法需要额外的对照实验,而这些实验容易出现系统误差。我们开发了利用方差稳定化评估显著性的方法,无需外部对照实验即可学习误差模型参数。该方法经过实验验证,比当前标准方法具有更高的灵敏度,并纳入了错误发现率分析。相应的软件(“Chipper”)可免费获取。本文所述方法应有助于揭示生物体的转录调控“线路图”。