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Record W3213337307 · doi:10.1038/s41467-021-26850-3

Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets

2021· article· en· W3213337307 on OpenAlexafffund
Ci Fu, Xiang Zhang, Amanda O. Veri, Kali R. Iyer, Emma Lash, Alice Xue, Huijuan Yan, Nicole M. Revie, Cassandra J. Wong, Zhen‐Yuan Lin, Elizabeth J. Polvi, Sean D. Liston, Benjamin VanderSluis, Jing Hou, Yoko Yashiroda, Anne‐Claude Gingras, Charles Boone, Teresa R. O’Meara, Matthew J. O’Meara, Suzanne M. Noble, Nicole Robbins, Chad L. Myers, Leah E. Cowen

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsSinai Health SystemLunenfeld-Tanenbaum Research InstituteUniversity of Toronto
FundersJapan Society for the Promotion of ScienceNational Institutes of HealthCanadian Institutes of Health ResearchGenome CanadaOntario GenomicsNational Institute of Allergy and Infectious DiseasesJapan Agency for Medical Research and DevelopmentCanadian Institute for Advanced ResearchFoundation for the National Institutes of Health
KeywordsCandida albicansComputational biologyAntifungalGenomeFunction (biology)BiologyGeneFungal pathogenTransfer RNAFunctional genomicsGenomicsGeneticsMicrobiologyRNA

Abstract

fetched live from OpenAlex

Fungal pathogens pose a global threat to human health, with Candida albicans among the leading killers. Systematic analysis of essential genes provides a powerful strategy to discover potential antifungal targets. Here, we build a machine learning model to generate genome-wide gene essentiality predictions for C. albicans and expand the largest functional genomics resource in this pathogen (the GRACE collection) by 866 genes. Using this model and chemogenomic analyses, we define the function of three uncharacterized essential genes with roles in kinetochore function, mitochondrial integrity, and translation, and identify the glutaminyl-tRNA synthetase Gln4 as the target of N-pyrimidinyl-β-thiophenylacrylamide (NP-BTA), an antifungal compound.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.361
Teacher spread0.331 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations84
Published2021
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicAntifungal resistance and susceptibilityFrench-language works237,207