Evidence map›Paper›PMID 33080209›Full record

ArticleCell systems2020

Mismatch-CRISPRi Reveals the Co-varying Expression-Fitness Relationships of Essential Genes in Escherichia coli and Bacillus subtilis.

John S Hawkins, Melanie R Silvis, Byoung-Mo Koo, Jason M Peters, Hendrik Osadnik, Marco Jost, Cameron C Hearne, Jonathan S Weissman, Horia Todor, Carol A Gross

Open access · bronzeAbstract read
In one paragraph

Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
6.1field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 143 citations in OpenAlex.

  1. Trial
  2. The phenotypic landscape of the model firmicuteProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Intracellular barriers and receptor masking limit success of abioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Systematic CRISPRi screening reveals genetic modulators ofbioRxiv : the preprint server for biology · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

25 more citing papers are in PubMed but not listed here.

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

10 authors at 3 institutions in 1 country.

John S HawkinsDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Melanie R SilvisDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Byoung-Mo KooDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Jason M PetersDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Hendrik OsadnikDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Marco JostDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Cameron C HearneDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Jonathan S WeissmanDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Horia TodorDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: horia.todor@gmail.com.
Carol A GrossDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute of Quantitative Biology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: cgrossucsf@gmail.com.
University of California, San Francisco · USHoward Hughes Medical Institute · USQB3 · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
GENETICS OF EUCARYOTIC AND PROCARYOTIC ORGANISMST32GM007810 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHRAFI, KAVEH, NARLIKAR, GEETA J · 1985 to 2020
$15.1M
PROJECT 3P50GM102706 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CATE, JAMIE H · 2012 to 2016
$9.5M
Cellular homeostasis pathways in bacteriaR35GM118061 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GROSS, CAROL ANNE · 2016 to 2025
$9.0M
Bay Area Cancer Target Discovery and Development NetworkU01CA168370 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCCORMICK, FRANK PATRICK, MCMANUS, MICHAEL T · 2012 to 2016
$3.9M
Harnessing CRISPR for Targeted and Inducible Epigenomic ReprogrammingR01DA036858 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A, QI, LEI STANLEY · 2013 to 2017
$2.9M
CRISPR-based Functional Genomics in Pathogenic BacteriaK22AI137122 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI PETERS, JASON M. · 2018 to 2019
$269k
Deciphering the logic of glycolipid signaling at the host-microbiome interfaceK99GM130964 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOST, MARCO · 2019 to 2020
$200k
Systematic Genome-Wide Characterization of Iron HomeostasisF32GM116331 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOST, MARCO · 2015 to 2017
$162k
Systematic Phenotypic Analysis of the Gram-positive EnvelopeF32GM108222 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PETERS, JASON M. · 2013 to 2016
$161k
Howard Hughes Medical InstituteNCI NIH HHS U01 CA168370NHGRI NIH HHS RM1 HG009490NIAID NIH HHS K22 AI137122NIDA NIH HHS R01 DA036858NIGMS NIH HHS F32 GM108222NIGMS NIH HHS F32 GM116331NIGMS NIH HHS K99 GM130964NIGMS NIH HHS P50 GM102706NIGMS NIH HHS R35 GM118061NIGMS NIH HHS T32 GM007810
6 · The paper itself

Abstract

Essential genes are the hubs of cellular networks, but lack of high-throughput methods for titrating gene expression has limited our understanding of the fitness landscapes against which their expression levels are optimized. We developed a modified CRISPRi system leveraging the predictable reduction in efficacy of imperfectly matched sgRNAs to generate defined levels of CRISPRi activity and demonstrated its broad applicability. Using libraries of mismatched sgRNAs predicted to span the full range of knockdown levels, we characterized the expression-fitness relationships of most essential genes in Escherichia coli and Bacillus subtilis. We find that these relationships vary widely from linear to bimodal but are similar within pathways. Notably, despite ∼2 billion years of evolutionary separation between E. coli and B. subtilis, most essential homologs have similar expression-fitness relationships with rare but informative differences. Thus, the expression levels of essential genes may reflect homeostatic or evolutionary constraints shared between the two organisms.

Indexed as

Bacillus subtilisBacterial ProteinsCRISPR-Cas SystemsEscherichia coliGene ExpressionGene Expression Regulation, BacterialGenes, EssentialGenetic FitnessBacterial ProteinsB. subtilisCRISRPiE. coliessential genesevolutionfunctional genomicsgene regulationsystems biology

Identifiers

PMID33080209
PMCPMC7704046
OpenAlexW3093163365

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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.