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Record W4416571000 · doi:10.1038/s41592-025-02939-1

Helixer: ab initio prediction of primary eukaryotic gene models combining deep learning and a hidden Markov model

2025· article· en· W4416571000 on OpenAlexaff
Felix Holst, Anthony Bolger, Felicitas Kindel, Christopher Günther, Janina Maß, Sebastian Triesch, Niklas Kiel, Nima P. Saadat, Oliver Ebenhöh, Björn Usadel, Rainer Schwacke, Andreas P.M. Weber, Marie Bolger, Alisandra K. Denton

Bibliographic record

VenueNature Methods · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Phylogenetic Studies
Canadian institutionsBureau de Coopération Interuniversitaire
FundersGerman Network for Bioinformatics InfrastructureHeinrich-Heine-Universität DüsseldorfForschungszentrum JülichBundesministerium für Bildung und ForschungDeutsche Forschungsgemeinschaft
KeywordsHidden Markov modelGene predictionIdentification (biology)Deep learningGenomeAnnotationSoftwareGene AnnotationGenome project

Abstract

fetched live from OpenAlex

The accurate identification of genes is vital for understanding biological function, yet this remains challenging across many newly sequenced or less-studied species. Here we present Helixer, an artificial intelligence-based tool for ab initio gene prediction that delivers highly accurate gene models across fungal, plant, vertebrate and invertebrate genomes. Unlike traditional methods, Helixer operates without requiring additional experimental data such as RNA sequencing, making it broadly applicable to diverse species. We show that Helixer's pretrained models achieve accuracy on par with or exceeding current tools, producing gene annotations that closely match expert-curated references across multiple evaluation metrics. Its design enables immediate use on genomes without retraining, providing an efficient, accessible solution for genome annotation in both research and applied settings. The tool is available as an open-source software for local installation via GitHub. An online web interface is also available as well as through the Galaxy ToolShed.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.389
Threshold uncertainty score0.608

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.014
GPT teacher head0.299
Teacher spread0.285 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations32
Published2025
Admission routes1
Has abstractyes

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