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Record W3138519498 · doi:10.1038/s41467-021-21883-0

The transcriptional landscape of Shh medulloblastoma

2021· article· en· W3138519498 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHedgehog Signaling Pathway Studies
Canadian institutionsUniversity of British ColumbiaToronto Western HospitalUniversity Health NetworkMcMaster UniversityCanada's Michael Smith Genome Sciences CentreSickKids FoundationBC Cancer AgencyMcGill Genome CentreHamilton General HospitalSimon Fraser UniversityMcGill University Health CentreMcGill UniversityPrincess Margaret Cancer CentreUniversity of CalgaryOntario Institute for Cancer ResearchAlberta Children's HospitalUniversity of TorontoHospital for Sick Children
FundersNational Center for Research ResourcesNational Institute of General Medical SciencesNational Cancer InstituteNational Human Genome Research InstituteNational Institute of Mental HealthCanadian Cancer Society Research InstituteNational Institutes of HealthNational Heart, Lung, and Blood InstituteBroad InstituteGenome British ColumbiaHospital for Sick ChildrenCancer Research UKNational Institute on Drug AbuseEntertainment Industry FoundationStand Up To CancerInstitute of GeneticsBrain Tumour CharityTerry Fox Research InstituteCanadian Institutes of Health ResearchGenome CanadaCompute CanadaGovernment of CanadaOntario Institute for Cancer ResearchCommon FundCancer Research SocietyNIH Office of the DirectorVan Andel Research InstituteUniversity of TorontoBrain Tumour ResearchNational Institute of Neurological Disorders and StrokeLeidosGovernment of OntarioAmerican Association for Cancer Research
KeywordsMedulloblastomaBiologyGLI2Sonic hedgehogPTCH1HedgehogTranscriptomeGeneGeneticsGNAS complex locusHedgehog signaling pathwayLoss functionComputational biologyCancer researchPhenotypeGene expression

Abstract

fetched live from OpenAlex

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.

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.

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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.809
Threshold uncertainty score0.187

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 head0.015
GPT teacher head0.285
Teacher spread0.270 · 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