Evidence map›Paper›PMID 31101858›Full record

ArticleScientific reports2019

Optimizing the dynamics of protein expression.

Jan-Hendrik Trösemeier, Sophia Rudorf, Holger Loessner, Benjamin Hofner, Andreas Reuter, Thomas Schulenborg, Ina Koch, Isabelle Bekeredjian-Ding, Reinhard Lipowsky, Christel Kamp

Erratum issuedAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Review
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  6. Review
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  17. Review
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  20. Learning the Regulatory Code of Gene Expression.Frontiers in molecular biosciences · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Jan-Hendrik TrösemeierDivision of Microbiology, Paul Ehrlich Institut, Langen, Germany.
Sophia RudorfMax Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, Potsdam, Germany.ORCID http://orcid.org/0000-0001-7653-3733
Holger LoessnerDivision of Microbiology, Paul Ehrlich Institut, Langen, Germany.
Benjamin HofnerDivision of Microbiology, Paul Ehrlich Institut, Langen, Germany.
Andreas ReuterDivision of Allergology, Paul Ehrlich Institut, Langen, Germany.ORCID http://orcid.org/0000-0002-6082-9000
Thomas SchulenborgDivision of Allergology, Paul Ehrlich Institut, Langen, Germany.ORCID http://orcid.org/0000-0003-1928-9441
Ina KochGoethe University Frankfurt, Institute of Computer Science, Molecular Bioinformatics, Frankfurt am Main, Germany.
Isabelle Bekeredjian-DingDivision of Microbiology, Paul Ehrlich Institut, Langen, Germany.ORCID http://orcid.org/0000-0001-6646-5888
Reinhard LipowskyMax Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, Potsdam, Germany.
Christel KampDivision of Microbiology, Paul Ehrlich Institut, Langen, Germany. christel.kamp@pei.de.ORCID http://orcid.org/0000-0001-9997-6772

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heterologously expressed genes require adaptation to the host organism to ensure adequate levels of protein synthesis, which is typically approached by replacing codons by the target organism's preferred codons. In view of frequently encountered suboptimal outcomes we introduce the codon-specific elongation model (COSEM) as an alternative concept. COSEM simulates ribosome dynamics during mRNA translation and informs about protein synthesis rates per mRNA in an organism- and context-dependent way. Protein synthesis rates from COSEM are integrated with further relevant covariates such as translation accuracy into a protein expression score that we use for codon optimization. The scoring algorithm further enables fine-tuning of protein expression including deoptimization and is implemented in the software OCTOPOS. The protein expression score produces competitive predictions on proteomic data from prokaryotic, eukaryotic, and human expression systems. In addition, we optimized and tested heterologous expression of manA and ova genes in Salmonella enterica serovar Typhimurium. Superiority over standard methodology was demonstrated by a threefold increase in protein yield compared to wildtype and commercially optimized sequences.

Indexed as

Protein BiosynthesisAlgorithmsCodonEscherichia coliGenes, BacterialGenes, FungalHEK293 CellsHumansModels, BiologicalPeptide Chain Elongation, TranslationalRecombinant ProteinsRibosomesRNA, MessengerSaccharomyces cerevisiaeSalmonella typhimuriumSoftwareCodonRecombinant ProteinsRNA, Messenger

Identifiers

PMID31101858
PMCPMC6525252

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.