ArticleGenome biology2023
Using protein-per-mRNA differences among human tissues in codon optimization.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- VaxLab: integrated platform for rapid multistrategy mRNA vaccine design.Experimental & molecular medicine · 2026Article
- Codon changes challenge PCR-based gene doping detection.Gene therapy · 2025Article
- mRNA Cancer Vaccines: From Pandemic Paradigm to Personalized Oncology Therapeutics.Cancer innovation · 2025Review
- Unconventional codon usage bias mediates mRNA translational dynamics in macrophages.PLoS biology · 2025Article
- A deep learning model trained on expressed transcripts across different tissue types reveals cell-type codon-optimization preferences.Nucleic acids research · 2025Article
- Translation of the downstream ORF from bicistronic mRNAs by human cells: Impact of codon usage and splicing in the upstream ORF.Protein science : a publication of the Protein Society · 2025Article
- CodonBERT: a BERT-based architecture tailored for codon optimization using the cross-attention mechanism.Bioinformatics (Oxford, England) · 2024Article
- Codon-optimization in gene therapy: promises, prospects and challenges.Frontiers in bioengineering and biotechnology · 2024Review
- Tailor made: the art of therapeutic mRNA design.Nature reviews. Drug discovery · 2024Review
- Analysis of codon usage bias of thioredoxin in apicomplexan protozoa.Parasites & vectors · 2023Article
- Human Tissues Exhibit Diverse Composition of Translation Machinery.International journal of molecular sciences · 2023Article
- Using protein-per-mRNA differences among human tissues in codon optimization.Genome biology · 2023Article
- Comparative analysis of codon usage patterns ofFrontiers in microbiology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCodon usage and nucleotide composition of coding sequences have profound effects on protein expression. However, while it is recognized that different tissues have distinct tRNA profiles and codon usages in their transcriptomes, the effect of tissue-specific codon optimality on protein synthesis remains elusive.
resultsWe leverage existing state-of-the-art transcriptomics and proteomics datasets from the GTEx project and the Human Protein Atlas to compute the protein-to-mRNA ratios of 36 human tissues. Using this as a proxy of translational efficiency, we build a machine learning model that identifies codons enriched or depleted in specific tissues. We detect two clusters of tissues with an opposite pattern of codon preferences. We then use these identified patterns for the development of CUSTOM, a codon optimizer algorithm which suggests a synonymous codon design in order to optimize protein production in a tissue-specific manner. In human cell-line models, we provide evidence that codon optimization should take into account particularities of the translational machinery of the tissues in which the target proteins are expressed and that our approach can design genes with tissue-optimized expression profiles.
conclusionsWe provide proof-of-concept evidence that codon preferences exist in tissue-specific protein synthesis and demonstrate its application to synthetic gene design. We show that CUSTOM can be of benefit in biological and biotechnological applications, such as in the design of tissue-targeted therapies and vaccines.
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