Kim Sinae, Tsai Jerry, Kagiampakis Ioannis, LiWang Patricia, Vannucci Marina
Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Bioinformatics. 2007 Jan 15;23(2):245-6. doi: 10.1093/bioinformatics/btl566. Epub 2006 Nov 14.
We present an application of Bayesian variable selection to the novel detection of sequence elements that confer negative design to protein structure and function. As an illustration, we analyze the different dimer interfaces between the CXCL8 chemokine family with the CCL4 and CCL2 chemokine families to discover the changes that disfavor CXCL8 of quaternary structure.
In comparison with known experimental results, our method identifies evolutionarily conserved sequence changes in the CC families that inhibit CXCL8 quaternary structure. Therefore, we find positive selection of negative design elements. Furthermore, our approach predicts that a two-residue deletion conserved in the CCL4 chemokine family disfavors CXCL8 dimerization.
The Matlab code for the Bayesian variable selection is freely available at http://stat.tamu.edu/~mvannucci/webpages/codes.html
我们展示了贝叶斯变量选择在新型检测赋予蛋白质结构和功能负向设计的序列元件中的应用。作为一个例证,我们分析了CXCL8趋化因子家族与CCL4和CCL2趋化因子家族之间不同的二聚体界面,以发现不利于CXCL8四级结构的变化。
与已知的实验结果相比,我们的方法识别出CC家族中抑制CXCL8四级结构的进化保守序列变化。因此,我们发现了负向设计元件的正选择。此外,我们的方法预测CCL4趋化因子家族中保守的两个残基缺失不利于CXCL8二聚化。
贝叶斯变量选择的Matlab代码可从http://stat.tamu.edu/~mvannucci/webpages/codes.html免费获取。