Brief Bioinform. 2014 Nov;15(6):1014-27. doi: 10.1093/bib/bbt062. Epub 2013 Sep 10.
Nucleosome positioning plays an essential role in cellular processes by modulating accessibility of DNA to proteins. Many computational models have been developed to predict genome-wide nucleosome positions from DNA sequences. Comparative analysis of predicted and experimental nucleosome positioning maps facilitates understanding the regulatory mechanisms of transcription and DNA replication. Therefore, a comprehensive evaluation of existing computational methods is important and useful for biologists to choose appropriate ones in their research. In this article, we carried out a performance comparison among eight widely used computational methods on four species including yeast, fruitfly, mouse and human. In particular, we compared these methods on different regions of each species such as gene sequences, promoters and 5'UTR exons. The experimental results show that the performances of the two latest versions of the thermodynamic model are relatively steadier than the other four methods. Moreover, these methods are workable on four species, but their performances decrease gradually from yeast to human, indicating that the fundamental mechanism of nucleosome positioning is conserved through the evolution process, but more and more factors participate in the determination of nucleosome positions, which leads to sophisticated regulation mechanisms.
核小体定位在调节 DNA 与蛋白质的可及性方面发挥着重要作用,从而影响细胞进程。许多计算模型已被开发出来,用于根据 DNA 序列预测全基因组核小体的位置。预测和实验核小体定位图谱的比较分析有助于理解转录和 DNA 复制的调控机制。因此,对现有计算方法进行全面评估对于生物学家在研究中选择合适的方法非常重要和有用。在本文中,我们在酵母、果蝇、小鼠和人类这四个物种上对八种广泛使用的计算方法进行了性能比较。特别是,我们在每个物种的不同区域(如基因序列、启动子和 5'UTR 外显子)比较了这些方法。实验结果表明,热力学模型的两个最新版本的性能比其他四种方法更为稳定。此外,这些方法适用于四个物种,但它们的性能从酵母到人类逐渐降低,这表明核小体定位的基本机制在进化过程中是保守的,但越来越多的因素参与了核小体位置的确定,从而导致了复杂的调控机制。