Evidence map›Paper›PMID 20653936›Full record

ArticleGenome biology2010

Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering.

Dwight Kuo, Kai Tan, Guy Zinman, Timothy Ravasi, Ziv Bar-Joseph, Trey Ideker

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
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  7. Antibiotics (Basel, Switzerland) · 2020
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  16. Milbemycins: more than efflux inhibitors for fungal pathogens.Antimicrobial agents and chemotherapy · 2013
    Article
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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

6 authors at 3 institutions in 2 countries.

Dwight KuoDepartment of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Kai Tan
Guy Zinman
Timothy Ravasi
Ziv Bar-Joseph
Trey Ideker
University of California, San Diego · USCarnegie Mellon University · USUniversity of Iowa · US

Funding

A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
Reconstructing dynamic regulatory networksR01GM085022 · NIGMS · CARNEGIE-MELLON UNIVERSITY · PI BAR-JOSEPH, ZIV · 2008 to 2011
$1.1M
NIEHS NIH HHS R01 ES014811NIGMS NIH HHS R01 GM085022
6 · The paper itself

Abstract

backgroundFungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure.

resultsConserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity.

conclusionsWe have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.

Indexed as

AlgorithmsEvolution, MolecularGenetic VariationBiological TransportCandidaCluster AnalysisConserved SequenceDrug ResistanceFluconazoleFungiGene Expression ProfilingGene Expression Regulation, FungalKluyveromycesMembrane Transport ProteinsRegulatory Sequences, Nucleic AcidRNA, MessengerFluconazoleMembrane Transport ProteinsRNA, MessengerSterols

Identifiers

PMID20653936
PMCPMC2926788
OpenAlexW2154150984

What OpenQuestion holds

Textmetadata
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.