Extracting transcription factor targets from ChIP-Seq data.

Extracting transcription factor targets from ChIP-Seq data.
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DOI:
10.1093/nar/gkp536
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发表时间:
2009-09
影响因子:
14.9
通讯作者:
Kaestner KH
Kaestner KH
中科院分区:
生物学2区
文献类型:
--
作者:
Tuteja G;White P;Schug J;Kaestner KH

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CHIP-SEQ技术将染色质免疫沉淀(CHIP)与大规模平行测序相结合,它正在迅速替换芯片芯片芯片,以识别转录因子结合事件的全基因组鉴定。从Chip-Seq产生的大量序列标签中识别有限区域是一项艰巨的任务。在这里,我们介绍了Glitr(目标区域的全局标识符),该(通过基于随机的对照样本(输入染色质)数据计算倍数变化,可以准确地识别目标数据中的丰富区域。 Glitr使用一种分类方法来识别具有峰高和折叠变化的芯片数据中的区域,而峰高和折叠变化不类似于输入样本中的区域。我们将Glitr与最近的几种方法进行了比较,并表明Glitr提高了灵敏度,以识别与给定转录因子的共有序列紧密匹配的结合区域,并且可以检测其他程序错过的真正的转录因子目标。我们还使用GLITR来解决测序深度的问题,并表明测序生物学复制比重新列出同一样本更能识别更大的结合区域。
ChIP-Seq technology, which combines chromatin immunoprecipitation (ChIP) with massively parallel sequencing, is rapidly replacing ChIP-on-chip for the genome-wide identification of transcription factor binding events. Identifying bound regions from the large number of sequence tags produced by ChIP-Seq is a challenging task. Here, we present GLITR (GLobal Identifier of Target Regions), which accurately identifies enriched regions in target data by calculating a fold-change based on random samples of control (input chromatin) data. GLITR uses a classification method to identify regions in ChIP data that have a peak height and fold-change which do not resemble regions in an input sample. We compare GLITR to several recent methods and show that GLITR has improved sensitivity for identifying bound regions closely matching the consensus sequence of a given transcription factor, and can detect bona fide transcription factor targets missed by other programs. We also use GLITR to address the issue of sequencing depth, and show that sequencing biological replicates identifies far more binding regions than re-sequencing the same sample.
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