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Record W4412817864 · doi:10.1101/2025.07.28.667289

BioTransformer 4.0 a comprehensive computational tool for small molecule metabolism prediction

2025· preprint· en· W4412817864 on OpenAlexaff
Siyang Tian, Yannick Djoumbou-Feunang, Eponine Oler, Fei Wang, Russell Greiner, Emma Palm, Emma Schymanski, Claudine Manach, David S. Wishart

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolomics and Mass Spectrometry Studies
Canadian institutionsAlberta Medical AssociationUniversity of Alberta
Fundersnot available
KeywordsComputer scienceComputational biologyChemistryBiology

Abstract

fetched live from OpenAlex

Abstract BioTransformer 4.0, the successor to BioTransformer 3.0, is a freely available in silico metabolism prediction tool. It integrates both knowledge-based and machine learning approaches to predict metabolites for small molecules using one of seven modules: abiotic, environmental, CYP450, phase II, enzyme commission-based, human gut microbial, and all human metabolism. It also provides a customizable sequence prediction module that allows users to simulate multi-step metabolic transformations by chaining among the first six different modules. BioTransformer 4.0 can make predictions more efficiently and accurately than the previous version, as it includes more than 130 new reaction rules, and also an optional validation module to improve the efficiency by restricting the number of predicted metabolites, due to their similarity among real human metabolites. We evaluated its performance by running the six-step all-human metabolism prediction on the DrugBank dataset of 2,457 known biotransformations, and the PhytoHub dataset of 633 known biotransformations – achieving recall values of 87.2% (resp., 91.6%) for the DrugBank (resp., PhytoHub) datasets.

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)0.002
metaresearch head score (Gemma)0.003
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 score0.017
Threshold uncertainty score0.057

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0020.003
Bibliometrics0.0020.001
Science and technology studies0.0010.000
Scholarly communication0.0020.001
Open science0.0030.002
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0170.005

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 head0.014
GPT teacher head0.231
Teacher spread0.217 · 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

Citations4
Published2025
Admission routes1
Has abstractyes

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