![]() ![]() We demonstrate that sequential context achieved via RNN may yield codon selection that is more similar to the host genome, therefore improving protein expression more than frequency-based approaches. Our tool can predict synonymous codons for synthetic genes toward optimal expression in Escherichia coli. The model uses a bidirectional long short-term memory-based architecture, allowing for the sequential context of codon usage in genes to be learned. We compile a dataset of over 7,000 non-redundant, high-expression, robust genes which are used for deep learning. In this paper, we propose a novel recurrent-neural-network based codon optimization tool, ICOR, that aims to learn codon usage bias on a genomic dataset of Escherichia coli. However, existing solutions are primarily based on choosing high-frequency codons only, neglecting the important effects of rare codons. Codon optimization of synthetic DNA sequences is important for heterologous expression. Although such synonymous codons do not alter the encoded amino acid sequence, their selection can dramatically affect the expression of the resulting protein. In protein sequences-as there are 61 sense codons but only 20 standard amino acids-most amino acids are encoded by more than one codon. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. ![]()
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