Evidence map›Paper›PMID 35476524›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Systems biology approach to functionally assess the

Charles J Norsigian, Heather A Danhof, Colleen K Brand, Firas S Midani, Jared T Broddrick, Tor C Savidge, Robert A Britton, Bernhard O Palsson, Jennifer K Spinler, Jonathan M Monk

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Multi-strain analysis ofmSystems · 2026
    Article
  2. Pangenome-GWAS analysis ofCanadian journal of microbiology · 2026
    Article
  3. Multi-strain Analysis ofbioRxiv : the preprint server for biology · 2025
    Article
  4. Yeast adapts to diverse ecological niches driven by genomics and metabolic reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Phenotypic analysis of variousApplied and environmental microbiology · 2025
    Article
  6. Unique growth and morphology properties of Clade 5bioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Article
  9. EmergingmSystems · 2025
    Article
  10. Phenotypic analysis of variousbioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Article
  13. Computational Insight into Intraspecies Distinctions inInternational journal of molecular sciences · 2023
    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

10 authors.

Charles J NorsigianDepartment of Bioengineering, University of California San Diego, La Jolla, CA 92039.
Heather A DanhofDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030.ORCID 0000-0002-6347-0021
Colleen K BrandDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030.
Firas S MidaniDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030.ORCID 0000-0002-2473-7758
Jared T BroddrickSpace Biosciences Research Branch, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035.
Tor C SavidgeDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Robert A BrittonDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030.
Bernhard O PalssonDepartment of Bioengineering, University of California San Diego, La Jolla, CA 92039.ORCID 0000-0003-2357-6785
Jennifer K SpinlerSpace Biosciences Research Branch, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035.
Jonathan M MonkDepartment of Bioengineering, University of California San Diego, La Jolla, CA 92039.ORCID 0000-0002-3895-8949

Funding

Tissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Geoffrey A Preidis · 2001 to 2026
$28.3M
Systems Biology Approach to Redefine Susceptibility Testing and Treatment of MDR Pathogens in the Context of Host ImmunityU01AI124316 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 2016 to 2020
$10.2M
Research Training in Pediatrics GastroenterolgyT32DK007664 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI DOUGLAS G BURRIN · 1991 to 2026
$8.4M
Decoding Antibiotic-induced Susceptibility to Clostridium difficile InfectionU01AI124290 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI BRITTON, ROBERT A, GAREY, KEVIN W · 2016 to 2020
$7.9M
Diet driven evolution of epidemic ribotypes of Clostridium difficileR01AI123278 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI BRITTON, ROBERT A · 2018 to 2022
$2.0M
Metabolic adaptation drives pathogenicity of C. difficile epidemic strain RT078F32AI136404 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI DANHOF, HEATHER A. · 2019 to 2021
$191k
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 1U01AI12429NIAID NIH HHS F32 AI136404NIAID NIH HHS R01 AI123278NIAID NIH HHS U01 AI124290NIAID NIH HHS U01 AI124316NIDDK NIH HHS P30 DK056338NIDDK NIH HHS T32 DK007664
6 · The paper itself

Abstract

Combatting Clostridioides difficile infections, a dominant cause of hospital-associated infections with incidence and resulting deaths increasing worldwide, is complicated by the frequent emergence of new virulent strains. Here, we employ whole-genome sequencing, high-throughput phenotypic screenings, and genome-scale models of metabolism to evaluate the genetic diversity of 451 strains of C. difficile. Constructing the C. difficile pangenome based on this set revealed 9,924 distinct gene clusters, of which 2,899 (29%) are defined as core, 2,968 (30%) are defined as unique, and the remaining 4,057 (41%) are defined as accessory. We develop a strain typing method, sequence typing by accessory genome (STAG), that identifies 176 genetically distinct groups of strains and allows for explicit interrogation of accessory gene content. Thirty-five strains representative of the overall set were experimentally profiled on 95 different nutrient sources, revealing 26 distinct growth profiles and unique nutrient preferences; 451 strain-specific genome scale models of metabolism were constructed, allowing us to computationally probe phenotypic diversity in 28,864 unique conditions. The models create a mechanistic link between the observed phenotypes and strain-specific genetic differences and exhibit an ability to correctly predict growth in 76% of measured cases. The typing and model predictions are used to identify and contextualize discriminating genetic features and phenotypes that may contribute to the emergence of new problematic strains.

Indexed as

Clostridioides difficileCross InfectionClostridioidesGenetic VariationHumansSystems BiologyClostridioides difficilemetabolic profilepangenomicsstrain typingsystems biology

Identifiers

PMID35476524
PMCPMC9170149

What OpenQuestion holds

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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.