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Record W4409238952 · doi:10.1101/2025.04.01.646674

Unsupervised Whole-Genome Representation Learning Captures Bacterial Phenotypes

2025· preprint· en· W4409238952 on OpenAlexaff
C Dufault, Alan M Moses

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Phylogenetic Studies
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsRepresentation (politics)PhenotypeGenomeComputational biologyArtificial intelligenceUnsupervised learningComputer scienceBiologyEvolutionary biologyGeneticsGene

Abstract

fetched live from OpenAlex

Abstract Shifting from hand-crafted to learned representations of data has revolutionized fields like natural language processing and computer vision. Despite this, current approaches to bacterial phenotype prediction from the genome rely on training machine learning models on hand-crafted features, often binary indicators or counts of the presence of different conserved genomic elements and protein domains. Defining these shared elements and domains as our “genomic element vocabulary”, we tokenize entire bacterial genomes as sequences of these conserved elements and take advantage of advances in long-context language modeling to perform self-supervised whole-genome representation learning (WGRL). Through multi-task pretraining on a phylogenetically diverse dataset of hundreds of thousands of bacterial genomes, we present a genomic language model which produces representations of input genomes with features predictive of a broad range of phenotypes. We assess the quality of the learned representations through k-nearest neighbours prediction of 25 bacterial phenotypes, finding our WGRL representations more predictive than standard protein domain presence/absence representations for 23/25 different phenotypes. We additionally find the WGRL representations are robust to both poor genome assembly quality and incompleteness. Through learning the relationships between evolutionarily conserved genomic elements with self-supervised long-context language modeling, we demonstrate the first approach for extracting general-purpose whole-genome representations while preserving gene order.

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)0.002
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 score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0010.001
Research integrity0.0010.001
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 head0.012
GPT teacher head0.225
Teacher spread0.213 · 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

Citations0
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenomics and Phylogenetic Studies→French-language works237,207→