ArticleNucleic acids research2023
Revealing determinants of translation efficiency via whole-gene codon randomization and machine learning.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Global translational reprogramming inVirulence · 2026Article
- Combinatorial Optimization of Protein Systems in Synthetic Cells.ACS synthetic biology · 2026Article
- seq2ribo: structure-aware integration of machine learning and simulation to predict ribosome location profiles from RNA sequences.Bioinformatics (Oxford, England) · 2026Article
- CodonMoE: DNA language models for codon-dependent mRNA prediction.Bioinformatics (Oxford, England) · 2026Article
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- seq2ribo: Structure-aware integration of machine learning and simulation to predict ribosome location profiles from RNA sequences.bioRxiv : the preprint server for biology · 2026Article
- Evolution and Functional Implications of Codon Usage Bias in Eukaryotes.Journal of molecular evolution · 2026Review
- Advancing the frontier of plant-based therapeutics: critical innovations in molecular farming and bioprocess Integration.Biotechnology letters · 2026Review
- Advancing codon language modeling with synonymous codon constrained masking.Nucleic acids research · 2026Article
- A slight mismatch between a gene's codon usage and the cellular tRNA supply is beneficial.Nature communications · 2026Article
- Flux sampling and context-specific genome-scale metabolic models for biotechnological applications.Trends in biotechnology · 2026Review
- Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.PLoS biology · 2025Article
- Base composition at the start of the coding sequence controls the balance between translation initiation and mRNA degradation in E. coli.Nucleic acids research · 2025Article
- mRNABERT: advancing mRNA sequence design with a universal language model and comprehensive dataset.Nature communications · 2025Article
- ARCADE: Controllable Codon Design from Foundation Models via Activation Engineering.bioRxiv : the preprint server for biology · 2025Article
- OPT: Codon optimize gene sequences for E. coli protein overexpression.Journal of molecular biology · 2025Article
- Why AGG is associated with high transgene output: passenger effects and their implications for transgene design.NAR genomics and bioinformatics · 2025Article
- Improving the generalization of protein expression models with mechanistic sequence information.Nucleic acids research · 2025Article
- A statistical-physics approach for codon usage optimisation.Computational and structural biotechnology journal · 2024Article
- Advances in mRNA LNP-Based Cancer Vaccines: Mechanisms, Formulation Aspects, Challenges, and Future Directions.Journal of personalized medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been known for decades that codon usage contributes to translation efficiency and hence to protein production levels. However, its role in protein synthesis is still only partly understood. This lack of understanding hampers the design of synthetic genes for efficient protein production. In this study, we generated a synonymous codon-randomized library of the complete coding sequence of red fluorescent protein. Protein production levels and the full coding sequences were determined for 1459 gene variants in Escherichia coli. Using different machine learning approaches, these data were used to reveal correlations between codon usage and protein production. Interestingly, protein production levels can be relatively accurately predicted (Pearson correlation of 0.762) by a Random Forest model that only relies on the sequence information of the first eight codons. In this region, close to the translation initiation site, mRNA secondary structure rather than Codon Adaptation Index (CAI) is the key determinant of protein production. This study clearly demonstrates the key role of codons at the start of the coding sequence. Furthermore, these results imply that commonly used CAI-based codon optimization of the full coding sequence is not a very effective strategy. One should rather focus on optimizing protein production via reducing mRNA secondary structure formation with the first few codons.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.