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Record W4413337880 · doi:10.1038/s41591-025-03901-6

AI-driven reclassification of multiple sclerosis progression

2025· article· en· W4413337880 on OpenAlexaff
Habib Ganjgahi, Dieter A. Häring, Piet Aarden, Gordon Graham, Yang Sun, Stephen Gardiner, Wendy Su, Claude Berge, Antje Bischof, Elizabeth Fisher, Laura Gaetano, Stefan Thoma, Bernd C. Kieseier, Thomas E. Nichols, Alan J. Thompson, Xavier Montalbán, Fred Lublin, Ludwig Kappos, Douglas L. Arnold, Robert A Bermel, Heinz Wiendl, Chris Holmes

Bibliographic record

VenueNature Medicine · 2025
Typearticle
Languageen
FieldMedicine
TopicMultiple Sclerosis Research Studies
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersUniversité de FribourgAlbert-Ludwigs-Universität Freiburg
KeywordsMultiple sclerosisDiseaseSubclinical infectionMedicineClinical trialCohortClinically isolated syndromeMagnetic resonance imagingInternal medicineBioinformaticsOncologyImmunologyRadiologyBiology

Abstract

fetched live from OpenAlex

Multiple sclerosis (MS) affects 2.9 million people. Traditional classification of MS into distinct subtypes poorly reflects its pathobiology and has limited value for prognosticating disease evolution and treatment response, thereby hampering drug discovery. Here we report a data-driven classification of MS disease evolution by analyzing a large clinical trial database (approximately 8,000 patients, 118,000 patient visits and more than 35,000 magnetic resonance imaging scans) using probabilistic machine learning. Four dimensions define MS disease states: physical disability, brain damage, relapse and subclinical disease activity. Early/mild/evolving (EME) MS and advanced MS represent two poles of a disease severity spectrum. Patients with EME MS show limited clinical impairment and minor brain damage. Transitions to advanced MS occur via brain damage accumulation through inflammatory states, with or without accompanying symptoms. Advanced MS is characterized by moderate to high disability levels, radiological disease burden and risk of disease progression independent of relapses, with little probability of returning to earlier MS states. We validated these results in an independent clinical trial database and a real-world cohort, totaling more than 4,000 patients with MS. Our findings support viewing MS as a disease continuum. We propose a streamlined disease classification to offer a unifying understanding of the disease, improve patient management and enhance drug discovery efficiency and precision.

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)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.659
Threshold uncertainty score0.531

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.062
GPT teacher head0.391
Teacher spread0.329 · 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 designObservational
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

Citations26
Published2025
Admission routes1
Has abstractyes

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