Improved alignment of nucleosome DNA sequences using a mixture model.
Improved alignment of nucleosome DNA sequences using a mixture model.
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使用混合模型改善了核小体DNA序列的比对。
DOI：
10.1093/nar/gki977
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发表时间：
2005
影响因子：
14.9
通讯作者：
Widom, J
中科院分区：
文献类型：
--
作者：
Wang, JPZ;Widom, J
存在于核小体中的DNA序列具有某些二核苷酸信号的优选的100 bp周期性，但是核小体DNA的整体序列相似性很弱，并且传统的多序列比对工具不能产生有意义的比对。我们开发了一个混合物模型，其特征在于已知的二核苷酸周期性概率提高核小体DNA的比对。我们假设任何类型的周期性二核苷酸信号根据一系列“热点”周围的概率分布发射，这些热点沿着核小体DNA以10 bp的周期等距分布，但在核小体的中间具有1 bp的相移。我们同时对三个统计上最显著的二核苷酸信号AA/TT、GC和TA进行建模，同时允许信号之间的相移。通过同时最大化沃森和克里克链的可能性来获得比对。177个鸡核小体DNA序列的比对结果显示，所有10个不同的二核苷酸是周期性的，然而，只有两个不同的阶段和不同的强度。通过傅立叶分析，我们表明，我们的新的比对增强了周期性和序列的一致性相比，中心比对。核小体DNA序列比对的意义是通过将其与使用相同模型对非核小体序列获得的比对进行比较来评估的。
DNA sequences that are present in nucleosomes have a preferential ∼10 bp periodicity of certain dinucleotide signals, but the overall sequence similarity of the nucleosomal DNA is weak, and traditional multiple sequence alignment tools fail to yield meaningful alignments. We develop a mixture model that characterizes the known dinucleotide periodicity probabilistically to improve the alignment of nucleosomal DNAs. We assume that a periodic dinucleotide signal of any type emits according to a probability distribution around a series of ‘hot spots’ that are equally spaced along nucleosomal DNA with 10 bp period, but with a 1 bp phase shift across the middle of the nucleosome. We model the three statistically most significant dinucleotide signals, AA/TT, GC and TA, simultaneously, while allowing phase shifts between the signals. The alignment is obtained by maximizing the likelihood of both Watson and Crick strands simultaneously. The resulting alignment of 177 chicken nucleosomal DNA sequences revealed that all 10 distinct dinucleotides are periodic, however, with only two distinct phases and varying intensity. By Fourier analysis, we show that our new alignment has enhanced periodicity and sequence identity compared with center alignment. The significance of the nucleosomal DNA sequence alignment is evaluated by comparing it with that obtained using the same model on non-nucleosomal sequences.
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