title: Multi-omics data driven analysis establishes reference codon biases for synthetic gene design in microbial and mammalian cells.
abstract: In this study, we analyzed multi-omics data and subsets thereof to establish reference codon usage biases for codon optimization in synthetic gene design. Specifically, publicly available genomic, transcriptomic, proteomic and translatomic data for microbial and mammalian expression hosts, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris and Chinese hamster ovary (CHO) cells, were compiled to derive their individual codon and codon pair frequencies. Then, host dependent and -omics specific codon biases were generated and compared by principal component analysis and hierarchical clustering. Interestingly, our results indicated the similar codon bias patterns of the highly expressed transcripts, highly abundant proteins, and efficiently translated mRNA in microbial cells, despite the general lack of correlation between mRNA and protein expression levels. However, for CHO cells, the codon bias patterns among various -omics subsets are not distinguishable, forming one cluster. Thus, we further investigated the effect of different input codon biases on codon optimized sequences using the codon context (CC) and individual codon usage (ICU) design parameters, via in silico case study on the expression of human IFNγ sequence in CHO cells. The results supported that CC is more robust design parameter than ICU for improved heterologous gene design.
authors: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors: Kok Siong
authors: KS
authors: Ang
authors: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors: Sarantos
authors: S
authors: Kyriakopoulos
authors: Sangon Biotech (Shanghai) Co., Ltd., 698 Xiangmin Road, SongJiang District, Shanghai 201611, China.
authors: Wei
authors: W
authors: Li
authors: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore. Electronic address: cheld@nus.edu.sg.
authors: Dong-Yup
authors: DY
authors: Lee
mesh_terms: D000818:Animals; D016466:CHO Cells; D003062:Codon; D003198:Computer Simulation; D003412:Cricetulus; D057225:Data Mining / Q000379:methods; D004926:Escherichia coli / Q000235:genetics; D023281:Genomics / Q000379:methods*; D008322:Mammals / Q000235:genetics*; D010843:Pichia / Q000235:genetics; D025341:Principal Component Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D003062:Codon
keywords: Codon optimization; Microbial and mammalian hosts; Multi-omics data; Reference codon bias; Synthetic gene design