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Protein Biosynthesis

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Revealing determinants of translation efficiency via whole-gene codon randomization and machine learning.

Nucleic acids research
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 synt...

Predicting functional consequences of SNPs on mRNA translation via machine learning.

Nucleic acids research
The functional impact of single nucleotide polymorphisms (SNPs) on translation has yet to be considered when prioritizing disease-causing SNPs from genome-wide association studies (GWAS). Here we apply machine learning models to genome-wide ribosome ...

Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides.

Nature communications
Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are required to validate candidates in high throughput and at low...

Integrated multiplexed assays of variant effect reveal determinants of catechol-O-methyltransferase gene expression.

Molecular systems biology
Multiplexed assays of variant effect are powerful methods to profile the consequences of rare variants on gene expression and organismal fitness. Yet, few studies have integrated several multiplexed assays to map variant effects on gene expression in...

Prioritization of genes for translation: a computational approach.

Expert review of proteomics
INTRODUCTION: Gene identification for genetic diseases is critical for the development of new diagnostic approaches and personalized treatment options. Prioritization of gene translation is an important consideration in the molecular biology field, a...

Optimizing 5'UTRs for mRNA-delivered gene editing using deep learning.

Nature communications
mRNA therapeutics are revolutionizing the pharmaceutical industry, but methods to optimize the primary sequence for increased expression are still lacking. Here, we design 5'UTRs for efficient mRNA translation using deep learning. We perform polysome...

Transfer learning for cross-context prediction of protein expression from 5'UTR sequence.

Nucleic acids research
Model-guided DNA sequence design can accelerate the reprogramming of living cells. It allows us to engineer more complex biological systems by removing the need to physically assemble and test each potential design. While mechanistic models of gene e...

Current limitations in predicting mRNA translation with deep learning models.

Genome biology
BACKGROUND: The design of nucleotide sequences with defined properties is a long-standing problem in bioengineering. An important application is protein expression, be it in the context of research or the production of mRNA vaccines. The rate of prot...

Predicting synthetic mRNA stability using massively parallel kinetic measurements, biophysical modeling, and machine learning.

Nature communications
mRNA degradation is a central process that affects all gene expression levels, though it remains challenging to predict the stability of a mRNA from its sequence, due to the many coupled interactions that control degradation rate. Here, we carried ou...

Predicting photosynthetic bacteria-derived protein synthesis from wastewater using machine learning and causal inference.

Bioresource technology
Causal inference-assisted machine learning was used to predict photosynthetic bacterial (PSB) protein production capacity and identify key factors. The extreme gradient boosting algorithm effectively predicted protein content, while the gradient boos...