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Record W4403569762 · doi:10.1101/2024.10.18.24315503

Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy

2024· preprint· en· W4403569762 on OpenAlexaff
Kelly Blacklock, Kevin S. Donnelly, Yuting Lu, Jorge del Pozo, Laura Glendinning, Gerry Polton, Laura E. Selmic, Jean‐Benoit Tanis, David Killick, Maciej Parys, Joanna R. Morris, Inge Breathnach, Sara Gould, Darren J. Shaw, Mickey Tivers, Davide Malucelli, Ana Paula Marques, Katarzyna Purzycka, Matteo Cantatore, Marie E. Mathers, Mark Stares, Alison Meynert, E. Elizabeth Patton

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldVeterinary
TopicInfectious Diseases and Mycology
Canadian institutionsMinnow Environmental (Canada)
Fundersnot available
KeywordsMelanomaMucosal melanomaMedicineDermatologyBiologyCancer research

Abstract

fetched live from OpenAlex

Abstract Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for pre-clinical trials. Comprehensive data on this tumour type is scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma to determine whether the common canine disease could inform the rare human equivalent. Using a human and canine primary oronasal mucosal melanoma (OMM) cohort of treatment naive archival tissue, alongside clinicopathological data, we obtained transcriptomic immunohistochemical, and microbiome data from both species. We defined the transcriptomic landscape in both species, and linked our findings to immunohistochemical, microbiome and clinical data. Human and dog OMM stratified into two distinctive transcriptional groups which we defined using a species-independent 41-gene signature. These two subgroups are termed CTLA4-high and cMET-high, and indicate actionable targets for OMM patients. To guide clinical decision-making, we developed immunohistochemical diagnostic tools which distinguish between transcriptomic subgroups. For the first time, we find that OMM has conserved transcriptomic subtypes and biological similarity between the canine and human OMM, with significant implications for patient classification, treatment, and clinical trial design.

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 score0.024
Threshold uncertainty score0.884

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 head0.044
GPT teacher head0.328
Teacher spread0.285 · 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

Citations0
Published2024
Admission routes1
Has abstractyes

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