MMDiff: quantitative testing for shape changes in ChIP-Seq data sets.
MMDiff: quantitative testing for shape changes in ChIP-Seq data sets.
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DOI：
10.1186/1471-2164-14-826
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发表时间：
2013-11-24
期刊：
影响因子：
4.4
通讯作者：
Sanguinetti G
中科院分区：
文献类型：
--
作者：
Schweikert G;Cseke B;Clouaire T;Bird A;Sanguinetti G
细胞特异性基因表达受表观遗传修饰和转录因子结合控制。虽然这些蛋白质-DNA相互作用的全基因组图谱已经广泛使用，但由此产生的ChIP-Seq数据集的定量比较仍然具有挑战性。目前检测差异结合或修饰区域的方法主要借用自RNA-Seq数据分析，因此重点关注映射到区域的片段总数，忽略峰形状中编码的任何信息。在这里，我们提出了MMDiff，一个强大的，广泛适用的方法检测序列计数数据集之间的差异。基于量化信号轮廓中的形状变化，它克服了数据的高度结构化性质和重复数据的缺乏所带来的挑战。我们首先使用一个模拟的数据集比较MMDiff的性能与四种替代方法获得的结果。我们证明，MMDiff优于峰型样品之间的变化时。接下来，我们使用MMDiff重新分析组蛋白修饰H3 K4 me 3的最近数据集，阐明了这个突出的表观基因组标记的建立。我们的实证分析表明，该方法在实验中产生可重复的结果，并且能够检测组蛋白修饰中的功能重要变化。为了进一步探索MMDiff更广泛的适用性，我们将其应用于两个ENCODE数据集：一个研究组蛋白修饰H3 K27 ac，另一个测量转录因子CTCF的全基因组结合。在这两种情况下，MMDiff被证明是对基于计数的方法的补充。此外，我们可以表明，MMDiff是能够直接检测在邻近的结合位点的同型结合事件的变化。MMDiff可作为Bioconductor软件包随时使用。我们的研究结果表明，ChIP-Seq峰的高阶特征携带与总计数相关且通常互补的信息，因此在评估差异组蛋白修饰和转录因子结合方面很重要。我们已经开发了一种新的计算方法，MMDiff，能够探索这些功能，从而弥补了ChIP-Seq数据集分析中存在的差距。
Cell-specific gene expression is controlled by epigenetic modifications and transcription factor binding. While genome-wide maps for these protein-DNA interactions have become widely available, quantitative comparison of the resulting ChIP-Seq data sets remains challenging. Current approaches to detect differentially bound or modified regions are mainly borrowed from RNA-Seq data analysis, thus focusing on total counts of fragments mapped to a region, ignoring any information encoded in the shape of the peaks. Here, we present MMDiff, a robust, broadly applicable method for detecting differences between sequence count data sets. Based on quantifying shape changes in signal profiles, it overcomes challenges imposed by the highly structured nature of the data and the paucity of replicates. We first use a simulated data set to compare the performance of MMDiff with results obtained by four alternative methods. We demonstrate that MMDiff excels when peak profiles change between samples. We next use MMDiff to re-analyse a recent data set of the histone modification H3K4me3 elucidating the establishment of this prominent epigenomic marker. Our empirical analysis shows that the method yields reproducible results across experiments, and is able to detect functional important changes in histone modifications. To further explore the broader applicability of MMDiff, we apply it to two ENCODE data sets: one investigating the histone modification H3K27ac and one measuring the genome-wide binding of the transcription factor CTCF. In both cases, MMDiff proves to be complementary to count-based methods. In addition, we can show that MMDiff is capable of directly detecting changes of homotypic binding events at neighbouring binding sites. MMDiff is readily available as a Bioconductor package. Our results demonstrate that higher order features of ChIP-Seq peaks carry relevant and often complementary information to total counts, and hence are important in assessing differential histone modifications and transcription factor binding. We have developed a new computational method, MMDiff, that is capable of exploring these features and therefore closes an existing gap in the analysis of ChIP-Seq data sets.
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DOI：
10.1093/biostatistics/kxr054
发表时间：
2012-04
期刊：
Biostatistics (Oxford, England)
影响因子：
--
作者：
Hansen KD;Irizarry RA;Wu Z
通讯作者：
Wu Z
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影响因子：
64.8
作者：
Ross-Innes, Caryn S.;Stark, Rory;Teschendorff, Andrew E.;Holmes, Kelly A.;Ali, H. Raza;Dunning, Mark J.;Brown, Gordon D.;Gojis, Ondrej;Ellis, Ian O.;Green, Andrew R.;Ali, Simak;Chin, Suet-Feung;Palmieri, Carlo;Caldas, Carlos;Carroll, Jason S.
通讯作者：
Carroll, Jason S.
影响因子：
12.3
作者：
Robinson MD;Oshlack A
通讯作者：
Oshlack A
影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
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Wong, Wing H.
人胚胎干细胞来源的雷特综合征神经元的全局转录和翻译抑制。
影响因子：
23.9
作者：
Li, Yun;Wang, Haoyi;Muffat, Julien;Cheng, Albert W.;Orlando, David A.;Loven, Jakob;Kwok, Show-ming;Feldman, Danielle A.;Bateup, Helen S.;Gao, Qing;Hockemeyer, Dirk;Mitalipova, Maisam;Lewis, Caroline A.;Vander Heiden, Matthew G.;Sur, Mriganka;Young, Richard A.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf