Multi-omics data driven analysis establishes reference codon biases for synthetic gene design in microbial and mammalian cells
| Autor: | Dong-Yup Lee, Wei Li, Sarantos Kyriakopoulos, Kok Siong Ang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
In silico Context (language use) CHO Cells Saccharomyces cerevisiae Pichia General Biochemistry Genetics and Molecular Biology Pichia pastoris Transcriptome 03 medical and health sciences Cricetulus Escherichia coli Animals Data Mining Computer Simulation Codon Molecular Biology Gene Mammals Genetics Principal Component Analysis Messenger RNA biology Chinese hamster ovary cell Genomics biology.organism_classification 030104 developmental biology Codon usage bias |
| Zdroj: | Methods. 102:26-35 |
| ISSN: | 1046-2023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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