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Record W2950863675 · doi:10.3389/fchem.2019.00402

GLORY: Generator of the Structures of Likely Cytochrome P450 Metabolites Based on Predicted Sites of Metabolism

2019· article· en· W2950863675 on OpenAlexfundno aff
Christina de Bruyn Kops, Conrad Stork, Martin Šícho, Nikolay Kochev, Daniel Svozil, Nina Jeliazkova, Johannes Kirchmair

Bibliographic record

VenueFrontiers in Chemistry · 2019
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsnot available
FundersBergens ForskningsstiftelseMinistry of Education, Youth and ScienceDeutsche ForschungsgemeinschaftUniversity of Alberta
KeywordsGloryXenobioticMetaboliteComputer scienceCytochrome P450Drug metabolismCheminformaticsComputational biologyChemistryMetabolismBiochemistryBiologyComputational chemistryEnzyme

Abstract

fetched live from OpenAlex

Computational prediction of xenobiotic metabolism can provide valuable information to guide the development of drugs, cosmetics, agrochemicals, and other chemical entities. We have previously developed FAME 2, an effective tool for predicting sites of metabolism (SoMs). In this work, we focus on the prediction of the chemical structures of metabolites, in particular metabolites of xenobiotics. To this end, we have developed a new tool, GLORY, which combines SoM prediction with FAME 2 and a new collection of rules for metabolic reactions mediated by the cytochrome P450 enzyme family. GLORY has two modes: MaxEfficiency and MaxCoverage. For MaxEfficiency mode, the use of predicted SoMs to restrict the locations in the molecule at which the reaction rules could be applied was explored. For MaxCoverage mode, the predicted SoM probabilities were instead used to develop a new scoring approach for the predicted metabolites. With this scoring approach, GLORY achieves a recall of 0.83 and can predict at least one known metabolite within the top three ranked positions for 76% of the molecules of a new, manually curated test set. GLORY is freely available as a web server at https://acm.zbh.uni-hamburg.de/glory/, and the datasets and reaction rules are provided in the Supplementary Material.

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)0.005
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: Methods · Consensus signal: Methods
Teacher disagreement score0.015
Threshold uncertainty score0.049

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.005
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0030.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0020.001
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0150.004

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 head0.007
GPT teacher head0.228
Teacher spread0.221 · 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
GenreMethods

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

Citations80
Published2019
Admission routes1
Has abstractyes

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