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Reveal Principles of Codon Optimization via Machine Learning

Deng, F.; Li, H.; Sun, D.; Duan, G.; Sun, Z.; Xue, G.

2026-04-21 bioinformatics
10.64898/2026.04.16.718958 bioRxiv
Show abstract

High level of protein expression is usually welcomed in industry and research, and codon optimization is widely used to achieve high expression. Methods of implementing codon optimization can be divided into two branches, one is classical methods which develop cost functions based on empirical law, another is AI methods which learn the codon choice principles from endogenous genes with neural networks. Here we develop two codon optimization tools based on two branches respectively, namely OptimWiz 2.1 and OptimWiz 3.0. Results of fusion protein fluorescence detection indicate that both OptimWiz 2.1 and OptimWiz 3.0 are superior to all the other commercially available codon optimization tools. Principles of codon optimization are revealed in the process of machine learning on both tools.

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