Picking ChIP-seq peak detectors for analyzing chromatin modification experiments.

Picking ChIP-seq peak detectors for analyzing chromatin modification experiments.
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DOI:
10.1093/nar/gks048
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发表时间:
2012-05
影响因子:
14.9
通讯作者:
Kluger Y
Kluger Y
中科院分区:
生物学2区
文献类型:
--
作者:
Micsinai M;Parisi F;Strino F;Asp P;Dynlacht BD;Kluger Y

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人们已开发出多种算法来分析 ChIP-Seq 数据。然而,分析不同模式的 ChIP-Seq 信号(尤其是表观遗传标记)的复杂性仍然需要开发新算法并对现有方法进行客观比较。我们开发了 Qeseq,一种算法,用于检测 ChIP 读取密度相对于背景增加的区域。 Qseq 采用关键的新颖元素,例如迭代重新校准和读数的邻近连接来识别任何长度的富集区域。为了客观评估其相对于其他 14 个 ChIP-Seq 寻峰器的性能,我们设计了一种基于验证判别分析 (VDA) 的新颖方案,以最佳选择验证位点并生成两个验证数据集,这是迄今为止针对关键表观遗传标记的算法基准最全面的数据集。此外,我们系统地探索了这些算法中总共 315 种不同的参数配置,发现一个数据集中的最佳参数通常不能推广到其他数据集。尽管如此,默认参数显示出最稳定的性能,建议应该使用它们。这项研究还提供了一种可重复且可推广的方法,用于对高通量测序工具进行公正的比较分析,从而促进未来的算法开发。
Numerous algorithms have been developed to analyze ChIP-Seq data. However, the complexity of analyzing diverse patterns of ChIP-Seq signals, especially for epigenetic marks, still calls for the development of new algorithms and objective comparisons of existing methods. We developed Qeseq, an algorithm to detect regions of increased ChIP read density relative to background. Qeseq employs critical novel elements, such as iterative recalibration and neighbor joining of reads to identify enriched regions of any length. To objectively assess its performance relative to other 14 ChIP-Seq peak finders, we designed a novel protocol based on Validation Discriminant Analysis (VDA) to optimally select validation sites and generated two validation datasets, which are the most comprehensive to date for algorithmic benchmarking of key epigenetic marks. In addition, we systematically explored a total of 315 diverse parameter configurations from these algorithms and found that typically optimal parameters in one dataset do not generalize to other datasets. Nevertheless, default parameters show the most stable performance, suggesting that they should be used. This study also provides a reproducible and generalizable methodology for unbiased comparative analysis of high-throughput sequencing tools that can facilitate future algorithmic development.
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