Evidence map›Paper›PMID 41045936›Full record

ArticleCell systems2025

Dual CRISPRi-seq for genome-wide genetic interaction studies identifies key genes involved in the pneumococcal cell cycle.

Julien Dénéréaz, Elise Eray, Bimal Jana, Vincent de Bakker, Horia Todor, Tim van Opijnen, Xue Liu, Jan-Willem Veening

Abstract read
In one paragraph

Article in Cell systems, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
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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

8 authors.

Julien DénéréazDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
Elise ErayDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
Bimal JanaBroad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Vincent de BakkerDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Horia TodorDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Tim van OpijnenBroad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: tim.vanopijnen@childrens.harvard.edu.
Xue LiuDepartment of Pathogen Biology, International Cancer Center, Shenzhen University Medical School, Shenzhen 518060, China. Electronic address: xueliu@szu.edu.cn.
Jan-Willem VeeningDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: jan-willem.veening@unil.ch.

Funding

A priori adaptive evolution predictions for antibiotic resistance through genome-wide network analyses and machine learningR01AI148470 · NIAID · BOSTON COLLEGE · PI ORTIZ-MARQUEZ, JUAN CESAR FEDERICO, VAN OPIJNEN, TIM · 2020 to 2024
$2.0M
Pooled and dual-guided CRISPRi, a genome-wide tool for genetic interaction mapping in high-throughputR21AI156203 · NIAID · BOSTON COLLEGE · PI ORTIZ-MARQUEZ, JUAN CESAR FEDERICO · 2021 to 2022
$430k
NIAID NIH HHS R01 AI148470NIAID NIH HHS R21 AI156203
6 · The paper itself

Abstract

Uncovering genotype-phenotype relationships is hampered by genetic redundancy. For example, most genes in Streptococcus pneumoniae are non-essential under laboratory conditions. A powerful approach to unravel genetic redundancy is by identifying gene-gene interactions. We developed a broadly applicable dual CRISPRi-seq method and analysis pipeline to probe genetic interactions (GIs) genome-wide. A library of 869 dual single-guide RNAs (sgRNAs) targeting high-confidence operons was created, covering over 70% of the genetic elements in the pneumococcal genome. Testing these 378,015 unique combinations, 4,026 significant GIs were identified. Besides known GIs, we found previously unknown positive and negative interactions involving genes in fundamental cellular processes such as division and chromosome segregation. The presented methods and bioinformatic approaches can serve as a roadmap for genome-wide gene interaction studies in other organisms. All interactions are available for exploration via the Pneumococcal Genetic Interaction Network (PneumoGIN), which can serve as a starting point for new biological discoveries. A record of this paper's transparent peer review process is included in the supplemental information.

Indexed as

Cell CycleCRISPR-Cas SystemsStreptococcus pneumoniaeClustered Regularly Interspaced Short Palindromic RepeatsComputational BiologyGene Regulatory NetworksGenome, BacterialGenome-Wide Association StudyCRISPRi-seqdual sgRNAgenetic interactionsStreptococcus pneumoniae

Identifiers

PMID41045936
PMCPMC13653531

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.