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Record W4392302540 · doi:10.1016/j.xgen.2024.100511

Genomic evolution shapes prostate cancer disease type

2024· article· en· W4392302540 on OpenAlexafffund
Dan J. Woodcock, Atef Sahli, Ruxandra Teslo, Vinayak Bhandari, Andreas Gruber, Aleksandra Ziubroniewicz, Gunes Gundem, Yaobo Xu, Adam P. Butler, Ezequiel Anokian, Bernard J. Pope, Chol‐Hee Jung, Maxime Tarabichi, Stefan C. Dentro, James Henry Royston Farmery, Peter Van Loo, Anne Y. Warren, Vincent J. Gnanapragasam, Freddie C. Hamdy, G. Steven Bova, Christopher S. Foster, David E. Neal, Yong‐Jie Lu, Zsofia Kote‐Jarai, Michael Fraser, Robert G. Bristow, Paul C. Boutros, Anthony J. Costello, Niall M. Corcoran, Christopher M. Hovens, Charlie E. Massie, Andy G. Lynch, Daniel S. Brewer, Rosalind A. Eeles, Colin S. Cooper, David C. Wedge

Bibliographic record

VenueCell Genomics · 2024
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsUniversity of Toronto
FundersNational Cancer InstituteCancer Research UK Cambridge Institute, University of CambridgeNIHR Cambridge Biomedical Research CentreCanadian Institutes of Health ResearchSyöpäjärjestötNational Institutes of HealthH2020 Marie Skłodowska-Curie ActionsMasonic Charitable FoundationSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungProstate Cancer CanadaProstate Cancer UKNational Institute for Health and Care ResearchSigrid Juséliuksen SäätiöNational Cancer Research InstituteRoyal Marsden NHS Foundation TrustNational Health and Medical Research CouncilUniversity of St AndrewsHorizon 2020 Framework ProgrammeAcademy of FinlandUniversity of CambridgeWellcome TrustCancer Research UKHutchison Whampoa LimitedOntario Institute for Cancer ResearchFrancis Crick InstituteMedical Research CouncilCancer Prevention and Research Institute of Texas
KeywordsProstate cancerCancerBiologyDiseaseComputational biologyProstateSomatic evolution in cancerAndrogen receptorChromoplexyEvolutionary biologyCancer researchGeneticsMedicineInternal medicinePCA3

Abstract

fetched live from OpenAlex

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.021
GPT teacher head0.301
Teacher spread0.280 · 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 source (direct Gemma or distilled Codex), 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

Citations16
Published2024
Admission routes2
Has abstractyes

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