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Sequence-specific flexibility organization of splicing flanking sequence and prediction of splice sites in the human genome

Zuo, Yongchun, Zhang, Pengfei, Liu, Li, Li, Tao, Peng, Yong, Li, Guangpeng, Li, Qianzhong
Chromosome research 2014 v.22 no.3 pp. 321-334
DNA, bioinformatics, data collection, deformation, genome, histones, humans, hybrids, models, molecular dynamics, nucleosomes, prediction
More and more reported results of nucleosome positioning and histone modifications showed that DNA structure play a well-established role in splicing. In this study, a set of DNA geometric flexibility parameters originated from molecular dynamics (MD) simulations were introduced to discuss the structure organization around splice sites at the DNA level. The obtained profiles of specific flexibility/stiffness around splice sites indicated that the DNA physical-geometry deformation could be used as an alternative way to describe the splicing junction region. In combination with structural flexibility as discriminatory parameter, we developed a hybrid computational model for predicting potential splicing sites. And the better prediction performance was achieved when the benchmark dataset evaluated. Our results showed that the mechanical deformability character of a splice junction is closely correlated with both the splice site strength and structural information in its flanking sequences.