MétaCan
Menu
← Back to cohort
Record W4366782348 · doi:10.1101/2023.04.21.537703

A mobile CRISPRi collection enables genetic interaction studies for the essential genes of <i>Escherichia coli</i>

2023· preprint· en· W4366782348 on OpenAlexafffund
Kenneth Rachwalski, Megan M. Tu, Sean J. Madden, Drew Hansen, Eric D. Brown

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsMcMaster University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsBiologyGene knockdownGeneCRISPRCRISPR interferenceGeneticsRNA interferencePhenotypeCas9Computational biologyMobile genetic elementsEscherichia coliGenetic screenGenome editingPlasmidRNA

Abstract

fetched live from OpenAlex

Summary Ordered collections of precise gene deletions in E. coli and other model microbes have proven to be invaluable resources to study the dispensability of the non-essential genome in different environmental and genetic contexts. The dispensability of canonically essential genes, however, has been largely unstudied in such contexts. Advances in gene editing, in particular CRISPR interference (CRISPRi), have enabled depletion of essential cellular machinery to study the downstream effects on bacterial physiology. Here, we describe the construction of an ordered E. coli CRISPRi collection, designed to knock down the expression of 356 essential genes with the induction of a catalytically inactive Cas9, harbored on the conjugative plasmid pFD152, that also encodes for expression of specific guide RNA scaffolds. This mobile CRISPRi library can be conjugated into other ordered genetic libraries, to assess combined effects of essential gene knockdowns with non-essential gene deletions. As proof of concept, we probed cell envelope synthesis with two crosses. First, we crossed a deletion in the gene lpp with the entire CRISPRi library. Similarly, we crossed the CRISPRi knockdown of lolA with ∼4,000 deletion strains of the Keio collection. These experiments revealed a number of notable genetic interactions for the essential phenotype probed and, in particular, showed supressing interactions for the loci in question.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.290
Teacher spread0.273 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreMethods

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2023
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicCRISPR and Genetic Engineering→French-language works237,207→