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Record W3024801711 · doi:10.1186/s40478-020-00939-0

Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets

2020· article· en· W3024801711 on OpenAlexaff
Eric Prince, Ros Whelan, Andrew M. Donson, Susan Staulcup, Astrid C. Hengartner, Trinka Vijmasi, Chibueze Agwu, Kevin O. Lillehei, Nicholas K. Foreman, James M. Johnston, Luca Massimi, Richard C. E. Anderson, Mark M. Souweidane, Robert P. Naftel, David D. Limbrick, Gerald A. Grant, Toba N. Niazi, Roy Dudley, Lindsay Kilburn, Eric M. Jackson, George I. Jallo, Kevin Ginn, Amy Smith, Joshua J. Chern, Amy Lee, Annie Drapeau, Mark D. Krieger, Michael H. Handler, Todd C. Hankinson

Bibliographic record

VenueActa Neuropathologica Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicPituitary Gland Disorders and Treatments
Canadian institutionsMcGill University
FundersBrain Tumour CharityChildren's National HospitalNational Cancer InstituteChildren's Mercy HospitalJohns Hopkins UniversityVanderbilt University
KeywordsTranscriptomeCraniopharyngiomaDiseaseMedicineBiologyBioinformaticsComputational biologyGene expressionGenePathologyGeneticsEndocrinology

Abstract

fetched live from OpenAlex

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.957
Threshold uncertainty score0.509

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 head0.057
GPT teacher head0.309
Teacher spread0.251 · 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

Citations10
Published2020
Admission routes1
Has abstractyes

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