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Record W4327747318 · doi:10.1038/s41591-023-02221-x

Diagnostic classification of childhood cancer using multiscale transcriptomics

2023· article· en· W4327747318 on OpenAlexafffund
Federico Comitani, Joshua O. Nash, Sarah Cohen‐Gogo, Astra I. Chang, Timmy T. Wen, Anant Maheshwari, Bipasha Goyal, Earvin S. Tio, Kevin Tabatabaei, Chelsea Mayoh, Regis Zhao, Ben Ho, Ledia Brunga, John E. Lawrence, Petra Balogh, Adrienne M. Flanagan, Sarah A. Teichmann, Annie Huang, Vijay Ramaswamy, Johann Hitzler, Jonathan D. Wasserman, Rebecca A. Gladdy, Brendan C. Dickson, Uri Tabori, Mark J. Cowley, Sam Behjati, David Malkin, Anita Villani, Meredith S. Irwin, Adam Shlien

Bibliographic record

VenueNature Medicine · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsSinai Health SystemPrincess Margaret Cancer CentreLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalSickKids FoundationUniversity of TorontoHospital for Sick Children
FundersGarron Family Cancer CentreOntario Ministry of Research and InnovationSt. Baldrick's FoundationCanadian Institutes of Health ResearchHospital for Sick ChildrenV Foundation for Cancer Research
KeywordsChildhood cancerOptimal distinctiveness theoryComputational biologyCancerTranscriptomeClassifier (UML)BioinformaticsOncologyMedicineBiologyArtificial intelligenceComputer scienceInternal medicineGeneticsPsychologyGene expressionGene

Abstract

fetched live from OpenAlex

The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types.

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)0.001
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.664
Threshold uncertainty score0.379

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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 head0.015
GPT teacher head0.306
Teacher spread0.291 · 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

Citations45
Published2023
Admission routes2
Has abstractyes

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