Peak shape clustering reveals biological insights.
Peak shape clustering reveals biological insights.
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DOI：
10.1186/s12859-015-0787-6
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发表时间：
2015-10-28
影响因子：
3
通讯作者：
Riva L
中科院分区：
文献类型：
--
作者：
Cremona MA;Sangalli LM;Vantini S;Dellino GI;Pelicci PG;Secchi P;Riva L
ChIP-seq实验广泛用于检测和研究DNA-蛋白质相互作用，如转录因子结合和染色质修饰。然而，ChIP-seq数据的下游分析目前仅限于信号强度的评估和基因组中富集区域（峰）的检测。峰形的其他特征几乎总是被忽略，尽管ChIP-seq对不同蛋白质以及单个实验中的不同区域显示出显着差异。我们假设峰形的统计学显著差异可能具有功能作用和生物学意义。因此，我们设计了五个指数，能够总结峰的形状，我们采用多元聚类技术，根据其复杂性和强度的覆盖函数的峰分为几组。此外，我们的新型分析管道采用了一系列统计和生物信息学技术，将获得的峰形与几个独立的基因组数据集相关联，包括其他全基因组蛋白质-DNA图谱和基因表达实验。为了阐明峰形的意义，我们将我们的方法应用于红系转录因子加塔-1在K562细胞系和巨核细胞中的研究。我们的研究表明，ChIP-seq图谱包括关于除用于沉淀的蛋白质之外的其他蛋白质的结合的信息。特别是，峰形提供了新的见解合作转录调控，并与基因表达。本文的在线版本（doi：10.1186/s12859-015-0787-6）包含补充材料，可供授权用户使用。
ChIP-seq experiments are widely used to detect and study DNA-protein interactions, such as transcription factor binding and chromatin modifications. However, downstream analysis of ChIP-seq data is currently restricted to the evaluation of signal intensity and the detection of enriched regions (peaks) in the genome. Other features of peak shape are almost always neglected, despite the remarkable differences shown by ChIP-seq for different proteins, as well as by distinct regions in a single experiment. We hypothesize that statistically significant differences in peak shape might have a functional role and a biological meaning. Thus, we design five indices able to summarize peak shapes and we employ multivariate clustering techniques to divide peaks into groups according to both their complexity and the intensity of their coverage function. In addition, our novel analysis pipeline employs a range of statistical and bioinformatics techniques to relate the obtained peak shapes to several independent genomic datasets, including other genome-wide protein-DNA maps and gene expression experiments. To clarify the meaning of peak shape, we apply our methodology to the study of the erythroid transcription factor GATA-1 in K562 cell line and in megakaryocytes. Our study demonstrates that ChIP-seq profiles include information regarding the binding of other proteins beside the one used for precipitation. In particular, peak shape provides new insights into cooperative transcriptional regulation and is correlated to gene expression. The online version of this article (doi:10.1186/s12859-015-0787-6) contains supplementary material, which is available to authorized users.