Relative Codon Adaptation: A Generic Codon Bias Index for Prediction of Gene Expression
Relative Codon Adaptation: A Generic Codon Bias Index for Prediction of Gene Expression
复制标题
DOI：
10.1093/dnares/dsq012
复制
发表时间：
2010-06-01
期刊：
影响因子：
4.1
通讯作者：
Erill, Ivan
中科院分区：
文献类型：
--
作者：
Fox, Jesse M.;Erill, Ivan
由于密码子偏倚指数（CBI）在计算生物学中的广泛应用，其发展仍然是一个活跃的研究领域。最近，相对密码子使用偏差（RCBS）作为一种新颖的 CBI 被引入，能够在不使用参考集的情况下估计密码子偏差。当这个新指数应用于大肠杆菌和酿酒酵母时，原始出版物的作者得出结论，自然选择有利于短基因的更高表达和增强的密码子使用优化。在这里，我们表明这个结论是有缺陷的，并且基于对 RCBS 索引中短序列的内在偏差和用于 E. con 验证的小数据集偏差的系统监督。此外，我们揭示了如何纠正 RCBS 以产生有用的结果，以及如何将其基本原理（我们在此称为相对密码子适应（RCA））制作成一个强大的基于参考集的索引，该索引直接考虑基因组碱基组成。最后，我们表明，在 CAI 参考集上操作时，RCA 作为基因表达的预测指标优于密码子适应指数 (CAI)，并且在分析具有高突变偏差的基因组时，这种改进显着更大。
The development of codon bias indices (CBIs) remains an active field of research due to their myriad applications in computational biology. Recently, the relative codon usage bias (RCBS) was introduced as a novel CBI able to estimate codon bias without using a reference set. The results of this new index when applied to Escherichia con and Saccharomyces cerevisiae led the authors of the original publications to conclude that natural selection favours higher expression and enhanced codon usage optimization in short genes. Here, we show that this conclusion was flawed and based on the systematic oversight of an intrinsic bias for short sequences in the RCBS index and of biases in the small data sets used for validation in E. con. Furthermore, we reveal that how the RCBS can be corrected to produce useful results and how its underlying principle, which we here term relative codon adaptation (RCA), can be made into a powerful reference-set-based index that directly takes into account the genomic base composition. Finally, we show that RCA outperforms the codon adaptation index (CAI) as a predictor of gene expression when operating on the CAI reference set and that this improvement is significantly larger when analysing genomes with high mutational bias.