Evidence map›Paper›PMID 37679324›Full record

ArticleNature communications2023

A generalizable Cas9/sgRNA prediction model using machine transfer learning with small high-quality datasets.

Dalton T Ham, Tyler S Browne, Pooja N Banglorewala, Tyler L Wilson, Richard K Michael, Gregory B Gloor, David R Edgell

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
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 synthesis or guideline pooled it, 28 citations in OpenAlex.

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  17. ACS synthetic biology · 2023
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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

7 authors at 1 institution in 1 country.

Dalton T Ham *Department of Biochemistry, Schulich School of Medicine and Dentistry, London, ON, N6A5C1, Canada.
Tyler S Browne *Department of Biochemistry, Schulich School of Medicine and Dentistry, London, ON, N6A5C1, Canada.
Pooja N BanglorewalaDepartment of Biochemistry, Schulich School of Medicine and Dentistry, London, ON, N6A5C1, Canada.
Tyler L WilsonTesseraqt Optimization Inc, Toronto, ON, Canada.
Richard K MichaelTesseraqt Optimization Inc, Toronto, ON, Canada.
Gregory B GloorDepartment of Biochemistry, Schulich School of Medicine and Dentistry, London, ON, N6A5C1, Canada. ggloor@uwo.ca.ORCID http://orcid.org/0000-0001-5803-3380
David R EdgellDepartment of Biochemistry, Schulich School of Medicine and Dentistry, London, ON, N6A5C1, Canada. dedgell@uwo.ca.ORCID http://orcid.org/0000-0003-3858-6150
Western University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The CRISPR/Cas9 nuclease from Streptococcus pyogenes (SpCas9) can be used with single guide RNAs (sgRNAs) as a sequence-specific antimicrobial agent and as a genome-engineering tool. However, current bacterial sgRNA activity models struggle with accurate predictions and do not generalize well, possibly because the underlying datasets used to train the models do not accurately measure SpCas9/sgRNA activity and cannot distinguish on-target cleavage from toxicity. Here, we solve this problem by using a two-plasmid positive selection system to generate high-quality data that more accurately reports on SpCas9/sgRNA cleavage and that separates activity from toxicity. We develop a machine learning architecture (crisprHAL) that can be trained on existing datasets, that shows marked improvements in sgRNA activity prediction accuracy when transfer learning is used with small amounts of high-quality data, and that can generalize predictions to different bacteria. The crisprHAL model recapitulates known SpCas9/sgRNA-target DNA interactions and provides a pathway to a generalizable sgRNA bacterial activity prediction tool that will enable accurate antimicrobial and genome engineering applications.

Indexed as

CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas SystemsData AccuracyEndonucleasesMachine LearningEndonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37679324
PMCPMC10485023
OpenAlexW4386499154

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.