Evidence map›Paper›PMID 37898126›Full record

ArticleCell host & microbe2023

Unbiased discovery of natural sequence variants that influence fungal virulence.

Daniel Paiva Agustinho, Holly Leanne Brown, Guohua Chen, Elizabeth Anne Gaylord, Jennifer Geddes-McAlister, Michael Richard Brent, Tamara Lea Doering

Open access · greenAbstract read
In one paragraph

Article in Cell host & microbe, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Unisexual reproduction in the global human fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Unisexual reproduction in the global human fungal pathogenbioRxiv : the preprint server for biology · 2025
    Article
  4. Cryptococcus.Current biology : CB · 2025
    Review
  5. Article
  6. 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

7 authors at 2 institutions in 2 countries.

Daniel Paiva AgustinhoDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Holly Leanne BrownDepartment of Computer Science & Engineering, Washington University, St. Louis, MO 63130, USA.
Guohua ChenDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Elizabeth Anne GaylordDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jennifer Geddes-McAlisterDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
Michael Richard BrentDepartment of Computer Science & Engineering, Washington University, St. Louis, MO 63130, USA; Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: brent@wustl.edu.
Tamara Lea DoeringDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: doering@wustl.edu.
Washington University in St. Louis · USUniversity of Guelph · CA

Funding

TRAINING PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYT32GM007067 · NIGMS · WASHINGTON UNIVERSITY · PI TRUE-KROB, HEATHER L · 1985 to 2020
$20.4M
Training Program in Cellular and Molecular BiologyT32GM139774 · NIGMS · WASHINGTON UNIVERSITY · PI HEATHER L TRUE-KROB · 2021 to 2026
$6.7M
CAPSULE REGULATION AND VIRULENCE IN CRYPTOCOCCUS NEOFORMANSR01AI087794 · NIAID · WASHINGTON UNIVERSITY · PI BRENT, MICHAEL R, DOERING, TAMARA L · 2011 to 2020
$4.1M
Natural genomic variants that influence cryptococcal pathogenicityR01AI146320 · NIAID · WASHINGTON UNIVERSITY · PI DOERING, TAMARA L · 2020 to 2024
$3.0M
IDENTIFICATION OF NATURAL GENOMIC VARIANTS THAT INFLUENCE CRYPTOCOCCAL VIRULENCER21AI131206 · NIAID · WASHINGTON UNIVERSITY · PI BRENT, MICHAEL R, DOERING, TAMARA L · 2017 to 2018
$419k
NIAID NIH HHS R01 AI087794NIAID NIH HHS R01 AI146320NIAID NIH HHS R21 AI131206NIGMS NIH HHS T32 GM007067NIGMS NIH HHS T32 GM139774
6 · The paper itself

Abstract

Isolates of Cryptococcus neoformans, a fungal pathogen that kills over 112,000 people each year, differ from a 19-Mb reference genome at a few thousand up to almost a million DNA sequence positions. We used bulked segregant analysis and association analysis, genetic methods that require no prior knowledge of sequence function, to address the key question of which naturally occurring sequence variants influence fungal virulence. We identified a region containing such variants, prioritized them, and engineered strains to test our findings in a mouse model of infection. At one locus, we identified a 4-nt variant in the PDE2 gene that occurs in common laboratory strains and severely truncates the encoded phosphodiesterase. The resulting loss of phosphodiesterase activity significantly impacts virulence. Our studies demonstrate a powerful and unbiased strategy for identifying key genomic regions in the absence of prior information and provide significant sequence and strain resources to the community.

Indexed as

CryptococcosisCryptococcus neoformansAnimalsHumansMicePhosphoric Diester HydrolasesVirulenceVirulence FactorsPhosphoric Diester HydrolasesVirulence Factorsbulked segregant analysisCryptococcus neoformansnatural sequence variantsPde2

Identifiers

PMID37898126
PMCPMC10842055
OpenAlexW4388007017

What OpenQuestion holds

Textmetadata
LicenceTDM
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.