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Record W4400455337 · doi:10.1016/j.cell.2024.06.023

TULIPs decorate the three-dimensional genome of PFA ependymoma

2024· article· en· W4400455337 on OpenAlexaff
Michael J. Johnston, John J. Y. Lee, Bo Hu, Ana Nikolić, Elham Hasheminasabgorji, Audrey Baguette, Seungil Paik, Haifeng Chen, Sachin Kumar, Carol Chen, Selin Jessa, Polina Balin, Vernon Fong, Melissa Zwaig, Kulandaimanuvel Antony Michealraj, Xun Chen, Yanlin Zhang, Srinidhi Varadharajan, Pierre Billon, Nikoleta Juretic, Craig Daniels, Amulya Nageswara Rao, Caterina Giannini, Eric M. Thompson, Miklós Garami, Péter Hauser, Tímea Pócza, Young Ho Shin, Byung-Kyu Cho, Seung‐Ki Kim, Kyu‐Chang Wang, Ji Yeoun Lee, Wiesława Grajkowska, Marta Perek‐Polnik, Sameer Agnihotri, Stephen C. Mack, Benjamin Ellezam, Alexander G. Weil, Jeremy N. Rich, Guillaume Bourque, Jennifer A. Chan, V. Wee Yong, Mathieu Lupien, Jiannis Ragoussis, Claudia L. Kleinman, Jacek Majewski, Mathieu Blanchette, Nada Jabado, Michael D. Taylor, Marco Gallo

Bibliographic record

VenueCell · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Chromatin Dynamics
Canadian institutionsJewish General HospitalUniversity Health NetworkOntario Institute for Cancer ResearchCentre Hospitalier Universitaire Sainte-JustineHotchkiss Brain InstituteMontreal Neurological Institute and HospitalMcGill Genome CentreHospital for Sick ChildrenUniversité de MontréalMcGill UniversityMcGill University Health CentreUniversity of TorontoAlberta Children's HospitalPrincess Margaret Cancer CentreUniversity of Calgary
Fundersnot available
KeywordsBiologyGenomeEpendymomaUniversality (dynamical systems)Computational biologyEvolutionary biologyGeneticsGenePathology

Abstract

fetched live from OpenAlex

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

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)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.006
GPT teacher head0.203
Teacher spread0.197 · 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

Citations21
Published2024
Admission routes1
Has abstractno

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