Codon optimization with deep learning to enhance protein expression.

Journal: Scientific reports
Published Date:

Abstract

Heterologous expression is the main approach for recombinant protein production ingenetic synthesis, for which codon optimization is necessary. The existing optimization methods are based on biological indexes. In this paper, we propose a novel codon optimization method based on deep learning. First, we introduce the concept of codon boxes, via which DNA sequences can be recoded into codon box sequences while ignoring the order of bases. Then, the problem of codon optimization can be converted to sequence annotation of corresponding amino acids with codon boxes. The codon optimization models for Escherichia Coli were trained by the Bidirectional Long-Short-Term Memory Conditional Random Field. Theoretically, deep learning is a good method to obtain the distribution characteristics of DNA. In addition to the comparison of the codon adaptation index, protein expression experiments for plasmodium falciparumĀ candidate vaccine and polymerase acidic protein were implemented for comparison with the original sequences and the optimized sequences from Genewiz and ThermoFisher. The results show that our method for enhancing protein expression is efficient and competitive.

Authors

  • Hongguang Fu
    School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China.
  • Yanbing Liang
    University of Electronic Science and Technology of China, Chengdu, 611731, China.
  • Xiuqin Zhong
    University of Electronic Science and Technology of China, Chengdu, 611731, China. zhongxiuqin2009@gmail.com.
  • ZhiLing Pan
    State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Lei Huang
    School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China.
  • Hailin Zhang
  • Yang Xu
    Dermatological Department, Nan Chong Center Hospital, Nanchong, China.
  • Wei Zhou
    Department of Eye Function Laboratory, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
  • Zhong Liu
    Science and Technology on Information Systems Engineering Laboratory, College of Information System and Management, National University of Defense Technology, Changsha, Hunan, China.