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Record W4408034500 · doi:10.1038/s41591-024-03435-3

Rapid brain tumor classification from sparse epigenomic data

2025· article· en· W4408034500 on OpenAlexaff
Björn Brändl, Mara Steiger, Carolin Kubelt, Christian Rohrandt, Zhihan Zhu, Maximilian Evers, Gaojianyong Wang, Bernhard Schuldt, Ann‐Kristin Afflerbach, Derek A. Wong, Amy Lum, Skarphéðinn Halldórsson, Luna Djirackor, Henning Leske, Svetlana Magadeeva, Romualdas Smičius, Claudia Quedenau, Nils Ole Schmidt, Ulrich Schüller, Einar Osland Vik-Mo, Martin Proescholdt, Markus J. Riemenschneider, Gelareh Zadeh, Ole Ammerpohl, Stephen Yip, Michael Synowitz, Alena van Bömmel, Helene Kretzmer, Frank Müller

Bibliographic record

VenueNature Medicine · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health NetworkUniversity of British Columbia
FundersBundesministerium für Bildung und Forschung
KeywordsComputer scienceBrain biopsyLimitingDNA sequencingNanoporeArtificial intelligenceNanopore sequencingNeuropathologyLiquid biopsyEpigenomicsMachine learningComputational biologyCancerMedicineBiologyPathologyNanotechnologyDNABiopsyDNA methylationGeneInternal medicine

Abstract

fetched live from OpenAlex

Although the intraoperative molecular diagnosis of the approximately 100 known brain tumor entities described to date has been a goal of neuropathology for the past decade, achieving this within a clinically relevant timeframe of under 1 h after biopsy collection remains elusive. Advances in third-generation sequencing have brought this goal closer, but established machine learning techniques rely on computationally intensive methods, making them impractical for live diagnostic workflows in clinical applications. Here we present MethyLYZR, a naive Bayesian framework enabling fully tractable, live classification of cancer epigenomes. For evaluation, we used nanopore sequencing to classify over 200 brain tumor samples, including 10 sequenced in a clinical setting next to the operating room, achieving highly accurate results within 15 min of sequencing. MethyLYZR can be run in parallel with an ongoing nanopore experiment with negligible computational overhead. Therefore, the only limiting factors for even faster time to results are DNA extraction time and the nanopore sequencer's maximum parallel throughput. Although more evidence from prospective studies is needed, our study suggests the potential applicability of MethyLYZR for live molecular classification of nervous system malignancies using nanopore sequencing not only for the neurosurgical intraoperative use case but also for other oncologic indications and the classification of tumors from cell-free DNA in liquid biopsies.

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)0.000
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: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.665
Threshold uncertainty score0.343

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 head0.027
GPT teacher head0.321
Teacher spread0.293 · 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 designNot applicable
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

Citations29
Published2025
Admission routes1
Has abstractyes

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