Evidence map›Paper›PMID 25416953›Full record

ArticleCell2014

Unraveling the biology of a fungal meningitis pathogen using chemical genetics.

Jessica C S Brown, Justin Nelson, Benjamin VanderSluis, Raamesh Deshpande, Arielle Butts, Sarah Kagan, Itzhack Polacheck, Damian J Krysan, Chad L Myers, Hiten D Madhani

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Hijacking anaerobic metabolism to restore antibiotic efficacy inApplied and environmental microbiology · 2025
    Article
  5. Article
  6. Article
  7. Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Antifungal discovery.Current opinion in microbiology · 2022
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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 at 4 institutions in 2 countries.

Jessica C S BrownDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Justin NelsonDepartment of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Benjamin VanderSluisDepartment of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Raamesh DeshpandeDepartment of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Arielle ButtsDepartment of Chemistry, University of Rochester Medical Center, Rochester, NY 14643, USA.
Sarah KaganDepartment of Clinical Microbiology and Infection Diseases, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Itzhack PolacheckDepartment of Clinical Microbiology and Infection Diseases, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Damian J KrysanDepartment of Chemistry, University of Rochester Medical Center, Rochester, NY 14643, USA; Departments of Pediatrics and Microbiology/Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14643, USA.
Chad L MyersDepartment of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: cmyers@cs.umn.edu.
Hiten D MadhaniDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: hitenmadhani@gmail.com.
University of Minnesota · USHadassah Medical Center · ILUniversity of California, San Francisco · USUniversity of Rochester Medical Center · US

Funding

Rapid production of SARS-CoV-2 molecular clones using CRISPR-based yeast recombineeringR01AI100272 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MADHANI, HITEN D · 2012 to 2025
$11.3M
Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
Methods for large-scale analysis of chemical-genetic interactionsR01HG005084 · NHGRI · UNIVERSITY OF MINNESOTA · PI MYERS, CHAD L · 2010 to 2022
$2.9M
Chemical-genetic functional annotation of the genome of a meningitis pathogenR01AI099206 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MADHANI, HITEN D · 2012 to 2016
$2.2M
Regulation of Virulence of Cryptococcus neoformansR01AI096869 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MADHANI, HITEN D · 2012 to 2016
$1.9M
Sparse Structural Equation Models for Gene Networks and Chemical GenomicsR01GM104975 · NIGMS · UNIVERSITY OF MIAMI CORAL GABLES · PI CAI, XIAODONG · 2012 to 2016
$1.8M
Discovery and evaluation of fungicidal anti-cryptococcal moleculesR01AI091422 · NIAID · UNIVERSITY OF ROCHESTER · PI KRYSAN, DAMIAN J · 2010 to 2012
$1.2M
NHGRI NIH HHS 1R01HG005084NHGRI NIH HHS R01 HG005084NIAID NIH HHS 1R01AI091422NIAID NIH HHS 5R01AI099206NIAID NIH HHS R01 AI091422NIAID NIH HHS R01 AI096869NIAID NIH HHS R01 AI099206NIAID NIH HHS R01 AI100272NIAID NIH HHS T32 AI060537NIGMS NIH HHS 1R01GM04975NIGMS NIH HHS R01 GM104975
6 · The paper itself

Abstract

The fungal meningitis pathogen Cryptococcus neoformans is a central driver of mortality in HIV/AIDS. We report a genome-scale chemical genetic data map for this pathogen that quantifies the impact of 439 small-molecule challenges on 1,448 gene knockouts. We identified chemical phenotypes for 83% of mutants screened and at least one genetic response for each compound. C. neoformans chemical-genetic responses are largely distinct from orthologous published profiles of Saccharomyces cerevisiae, demonstrating the importance of pathogen-centered studies. We used the chemical-genetic matrix to predict novel pathogenicity genes, infer compound mode of action, and to develop an algorithm, O2M, that predicts antifungal synergies. These predictions were experimentally validated, thereby identifying virulence genes, a molecule that triggers G2/M arrest and inhibits the Cdc25 phosphatase, and many compounds that synergize with the antifungal drug fluconazole. Our work establishes a chemical-genetic foundation for approaching an infection responsible for greater than one-third of AIDS-related deaths.

Indexed as

AIDS-Related Opportunistic InfectionsAlgorithmsAnimalsAntifungal AgentsCryptococcus neoformansDrug DiscoveryGene Knockout TechniquesMicrobial Sensitivity TestsSaccharomyces cerevisiaeVirulence FactorsAntifungal AgentsVirulence Factors

Identifiers

PMID25416953
PMCPMC4243055
OpenAlexW2149579582

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.