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

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

2025Nature Methods35 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

Computer scienceHidden Markov modelGene predictionArtificial intelligenceIdentification (biology)Computational biologyDeep learningGenomeAnnotationMachine learningSoftwareGene AnnotationGenome projectGenomicsMarkov chainData miningGeneMarkov modelBiologyPredictive modellingModel buildingBioinformaticsAb initioExperimental dataSoftware toolVisualizationSupervised learningPattern recognition (psychology)Genomics and Phylogenetic StudiesBioinformatics and Genomic NetworksMachine Learning in Bioinformatics
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