Evidence map›Paper›PMID 28545477›Full record

ArticleGenome biology2017

Optimizing complex phenotypes through model-guided multiplex genome engineering.

Gleb Kuznetsov, Daniel B Goodman, Gabriel T Filsinger, Matthieu Landon, Nadin Rohland, John Aach, Marc J Lajoie, George M Church

Abstract read
In one paragraph

Article in Genome biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Genomically recodedbioRxiv : the preprint server for biology · 2024
    Article
  7. Article
  8. Engineered mRNA-ribosome fusions for facile biosynthesis of selenoproteins.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Review
  10. Article
  11. Enhancement of Activity and Thermostability of Keratinase FromFrontiers in bioengineering and biotechnology · 2021
    Article
  12. Article
  13. Article
  14. Article
  15. Adaptive evolution of genomically recodedProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  16. Rewriting the Genetic Code.Annual review of microbiology · 2017
    Review
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Gleb KuznetsovDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9317-0639
Daniel B GoodmanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Gabriel T FilsingerDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Matthieu LandonDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Nadin RohlandDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
John AachDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Marc J LajoieDepartment of Genetics, Harvard Medical School, Boston, MA, USA. mlajoie@uw.edu.
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu.

Funding

MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
NIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

We present a method for identifying genomic modifications that optimize a complex phenotype through multiplex genome engineering and predictive modeling. We apply our method to identify six single nucleotide mutations that recover 59% of the fitness defect exhibited by the 63-codon E. coli strain C321.∆A. By introducing targeted combinations of changes in multiplex we generate rich genotypic and phenotypic diversity and characterize clones using whole-genome sequencing and doubling time measurements. Regularized multivariate linear regression accurately quantifies individual allelic effects and overcomes bias from hitchhiking mutations and context-dependence of genome editing efficiency that would confound other strategies.

Indexed as

Genetic EngineeringGenomicsEscherichia coliGenetic VariationGenome, BacterialGenotypeMutationGenome engineeringPredictive modelingSynthetic organisms

Identifiers

PMID28545477
PMCPMC5445303

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.