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Record W4401392108 · doi:10.1038/s41408-024-01111-w

Identification of genetic subtypes in follicular lymphoma

2024· article· en· W4401392108 on OpenAlexafffund
Victoria Shelton, Rajesh Detroja, Ting Liu, Keren Isaev, Anjali Silva, Verena Passerini, Mehran Bakhtiari, Lourdes Calvente, Michael Hong, Michael Y. He, Saloni Modi, Samantha Hershenfeld, Maja Ludvigsen, Charlotte Madsen, Stephen Hamilton‐Dutoit, Francesco d’Amore, Marianne Brodtkorb, Nathalie A. Johnson, Tara Baetz, David P. LeBrun, Josh W. D. Tobin, Maher K. Gandhi, Andrew J. Mungall, Wei Xu, Susana Ben‐Neriah, Christian Steidl, Jan Delabie, Rosemarie Tremblay‐LeMay, Opeyemi A. Jegede, Oliver Weigert, Brad S. Kahl, Andrew M. Evens, Robert Kridel

Bibliographic record

VenueBlood Cancer Journal · 2024
Typearticle
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsCanada's Michael Smith Genome Sciences CentreJewish General HospitalVector InstitutePrincess Margaret Cancer CentreQueen's UniversityUniversity of TorontoUniversity Health Network
FundersNational Cancer InstituteTerry Fox Research InstituteGovernment of CanadaDeutsche ForschungsgemeinschaftNational Institutes of HealthPrincess Margaret Cancer FoundationLeukemia and Lymphoma Society of CanadaF. Hoffmann-La RocheGénome QuébecCanadian Institutes of Health ResearchElse Kröner-Fresenius-StiftungLeukemia and Lymphoma Society
KeywordsIdentification (biology)Follicular lymphomaLymphomaMedicineComputational biologyHematologyInternal medicineBiologyBioinformaticsImmunologyOncologyGeneticsPathology

Abstract

fetched live from OpenAlex

Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.188
Threshold uncertainty score0.216

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 head0.010
GPT teacher head0.280
Teacher spread0.269 · 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

Citations13
Published2024
Admission routes2
Has abstractyes

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