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基于小波的方法来挖掘调控区的表观基因组语言。

A wavelet-based method to exploit epigenomic language in the regulatory region.

机构信息

Department of Genetics, Institute for Diabetes, Obesity and Metabolism, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA and Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.

出版信息

Bioinformatics. 2014 Apr 1;30(7):908-14. doi: 10.1093/bioinformatics/btt467. Epub 2013 Oct 4.

Abstract

MOTIVATION

Epigenetic landscapes in the regulatory regions reflect binding condition of transcription factors and their co-factors. Identifying epigenetic condition and its variation is important in understanding condition-specific gene regulation. Computational approaches to explore complex multi-dimensional landscapes are needed.

RESULTS

To study epigenomic condition for gene regulation, we developed a method, AWNFR, to classify epigenomic landscapes based on the detected epigenomic landscapes. Assuming mixture of Gaussians for a nucleosome, the proposed method captures the shape of histone modification and identifies potential regulatory regions in the wavelet domain. For accuracy estimation as well as enhanced computational speed, we developed a novel algorithm based on down-sampling operation and footprint in wavelet. We showed the algorithmic advantages of AWNFR using the simulated data. AWNFR identified regulatory regions more effectively and accurately than the previous approaches with the epigenome data in mouse embryonic stem cells and human lung fibroblast cells (IMR90). Based on the detected epigenomic landscapes, AWNFR classified epigenomic status and studied epigenomic codes. We studied co-occurring histone marks and showed that AWNFR captures the epigenomic variation across time.

AVAILABILITY AND IMPLEMENTATION

The source code and supplemental document of AWNFR are available at http://wonk.med.upenn.edu/AWNFR.

摘要

动机

调控区域的表观遗传景观反映了转录因子及其共因子的结合状态。识别表观遗传状态及其变化对于理解特定条件下的基因调控非常重要。需要探索复杂多维景观的计算方法。

结果

为了研究基因调控的表观基因组条件,我们开发了一种方法 AWNFR,基于检测到的表观基因组景观对表观基因组景观进行分类。假设核小体为高斯混合,所提出的方法捕捉到组蛋白修饰的形状,并在小波域中识别潜在的调控区域。为了提高准确性和计算速度,我们在小波中开发了一种基于降采样操作和足迹的新算法。我们使用模拟数据展示了 AWNFR 的算法优势。与以前基于小鼠胚胎干细胞和人肺成纤维细胞 (IMR90) 中表观基因组数据的方法相比,AWNFR 更有效地识别了调控区域,并且更准确。基于检测到的表观基因组景观,AWNFR 对表观基因组状态进行分类并研究表观基因组代码。我们研究了共现的组蛋白标记,并表明 AWNFR 捕获了跨时间的表观遗传变化。

可用性和实现

AWNFR 的源代码和补充文档可在 http://wonk.med.upenn.edu/AWNFR 获得。

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