Evidence map›Paper›PMID 36309502›Full record

ArticleNature communications2022

Automated identification of sequence-tailored Cas9 proteins using massive metagenomic data.

Matteo Ciciani, Michele Demozzi, Eleonora Pedrazzoli, Elisabetta Visentin, Laura Pezzè, Lorenzo Federico Signorini, Aitor Blanco-Miguez, Moreno Zolfo, Francesco Asnicar, Antonio Casini and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

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  18. An optimized SpCas9 high-fidelity variant for direct protein delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  19. 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

12 authors.

Matteo CicianiDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.
Michele DemozziDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0002-4577-3694
Eleonora PedrazzoliDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0002-8420-2587
Elisabetta VisentinDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0001-6586-4123
Laura PezzèAlia Therapeutics, Trento, Italy.
Lorenzo Federico SignoriniDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0002-9727-1987
Aitor Blanco-MiguezDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0001-7386-5572
Moreno ZolfoDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0001-6661-4046
Francesco AsnicarDepartment of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0003-3732-1468
Antonio CasiniAlia Therapeutics, Trento, Italy.
Anna Cereseto *Department of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy. anna.cereseto@unitn.it.ORCID 0000-0003-4453-2597
Nicola Segata *Department of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy. nicola.segata@unitn.it.ORCID 0000-0002-1583-5794

Funding

Exploiting Public Metagenomic Data to Uncover Cancer-Microbiome RelationshipsR01CA230551 · NCI · GRADUATE SCHOOL OF PUBLIC HEALTH AND HEALTH POLICY · PI Levi Waldron · 2020 to 2026
$3.9M
Exploiting public metagenomic data to uncover cancer-microbiome relationshipsU01CA230551 · NCI · GRADUATE SCHOOL OF PUBLIC HEALTH AND HEALTH POLICY · PI WALDRON, LEVI · 2019 to 2019
$464k
NCI NIH HHS R01 CA230551NCI NIH HHS U01 CA230551
6 · The paper itself

Abstract

The identification of the protospacer adjacent motif (PAM) sequences of Cas9 nucleases is crucial for their exploitation in genome editing. Here we develop a computational pipeline that was used to interrogate a massively expanded dataset of metagenome and virome assemblies for accurate and comprehensive PAM predictions. This procedure allows the identification and isolation of sequence-tailored Cas9 nucleases by using the target sequence as bait. As proof of concept, starting from the disease-causing mutation P23H in the RHO gene, we find, isolate and experimentally validate a Cas9 which uses the mutated sequence as PAM. Our PAM prediction pipeline will be instrumental to generate a Cas9 nuclease repertoire responding to any PAM requirement.

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsEndonucleasesGene EditingMetagenomeRNA, Guide, CRISPR-Cas SystemsCRISPR-Associated Protein 9EndonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID36309502
PMCPMC9617884

What OpenQuestion holds

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LicenceCC BY
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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.