Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments.

Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments.
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DOI:
10.1093/nar/gkt1249
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发表时间:
2014-03
影响因子:
14.9
通讯作者:
Kellis M
Kellis M
中科院分区:
生物学2区
文献类型:
--
作者:
Kheradpour P;Kellis M

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技术的最新进展导致可用转录因子ChIP-seq和ChIP-chip数据集的数量急剧增加。了解这些数据集的基序内容是了解调控的潜在机制的重要一步。在这里,我们使用文献中精选的基序对427个人类ChIP-seq数据集进行了系统的基序分析,并使用五种已建立的基序发现工具重新发现。我们使用一个系统的管道来计算每个数据集中的基序富集,为在文献中发现的基序变体之间进行选择和标记潜在的有问题的数据集提供了一种原则性的方法。我们的分析证实了已知的特异性的56个分析的因素组中的41个,并揭示了潜在的辅助因子的图案。我们还使用细胞类型特异性结合来寻找在特定条件下活跃的因子。我们提供的资源既可以浏览少量的因素,也可以进行大规模的系统分析。我们在每个ENCODE数据集中提供了基序矩阵,实例和丰富。这里发现的基序已用于平行研究,以验证抗体的特异性,了解数据集之间的协同性,并测量个体和物种之间基序结合的变化。
Recent advances in technology have led to a dramatic increase in the number of available transcription factor ChIP-seq and ChIP-chip data sets. Understanding the motif content of these data sets is an important step in understanding the underlying mechanisms of regulation. Here we provide a systematic motif analysis for 427 human ChIP-seq data sets using motifs curated from the literature and also discovered de novo using five established motif discovery tools. We use a systematic pipeline for calculating motif enrichment in each data set, providing a principled way for choosing between motif variants found in the literature and for flagging potentially problematic data sets. Our analysis confirms the known specificity of 41 of the 56 analyzed factor groups and reveals motifs of potential cofactors. We also use cell type-specific binding to find factors active in specific conditions. The resource we provide is accessible both for browsing a small number of factors and for performing large-scale systematic analyses. We provide motif matrices, instances and enrichments in each of the ENCODE data sets. The motifs discovered here have been used in parallel studies to validate the specificity of antibodies, understand cooperativity between data sets and measure the variation of motif binding across individuals and species.
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