State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
J Theor Biol. 2014 Mar 7;344:19-30. doi: 10.1016/j.jtbi.2013.11.022. Epub 2013 Dec 4.
Codon optimized genes have two major advantages: they simplify de novo gene synthesis and increase the expression level in target hosts. Often they achieve this by altering codon usage in a given gene. Codon optimization is complex because it usually needs to achieve multiple opposing goals. In practice, finding an optimal sequence from the massive number of possible combinations of synonymous codons that can code for the same amino acid sequence is a challenging task. In this article, we introduce COStar, a D-star Lite-based dynamic search algorithm for codon optimization. The algorithm first maps the codon optimization problem into a weighted directed acyclic graph using a sliding window approach. Then, the D-star Lite algorithm is used to compute the shortest path from the start site to the target site in the resulting graph. Optimizing a gene is thus converted to a search in real-time for a shortest path in a generated graph. Using in silico experiments, the performance of the algorithm was shown by optimizing the different genes including the human genome. The results suggest that COStar is a promising codon optimization tool for de novo gene synthesis and heterologous gene expression.
它们简化了从头基因合成的过程，并提高了目标宿主中的表达水平。通常，它们通过改变给定基因中的密码子使用来实现这一点。密码子优化是一个复杂的过程，因为它通常需要实现多个相互矛盾的目标。在实践中，从可以编码相同氨基酸序列的同义密码子的大量可能组合中找到最佳序列是一项具有挑战性的任务。在本文中，我们介绍了 COStar，这是一种基于 D-star Lite 的密码子优化动态搜索算法。该算法首先使用滑动窗口方法将密码子优化问题映射到加权有向无环图上。然后，使用 D-star Lite 算法计算生成图中从起始点到目标点的最短路径。因此，优化基因就转化为在生成的图中实时搜索最短路径。通过对包括人类基因组在内的不同基因进行计算机模拟实验，验证了该算法的性能。结果表明，COStar 是一种有前途的从头基因合成和异源基因表达的密码子优化工具。
