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Record W2520931435 · doi:10.1038/ncomms12605

Mutational signatures of ionizing radiation in second malignancies

2016· article· en· W2520931435 on OpenAlex
Sam Behjati, Gunes Gundem, David C. Wedge, Nicola D. Roberts, Patrick Tarpey, Susanna L. Cooke, Peter Van Loo, Ludmil B. Alexandrov, Manasa Ramakrishna, Helen Davies, Serena Nik‐Zainal, Claire Hardy, Calli Latimer, Keiran Raine, Lucy Stebbings, Andy Menzies, David Jones, Rebecca Shepherd, Adam P. Butler, Jon W. Teague, Mette Jorgensen, Bhavisha Khatri, Nischalan Pillay, Adam Shlien, P. Andrew Futreal, Christophe Badie, Colin S. Cooper, Rosalind A. Eeles, Douglas F. Easton, Christopher S. Foster, David E. Neal, Daniel S. Brewer, Freddie C. Hamdy, Yong‐Jie Lu, Andy G. Lynch, Charlie E. Massi, Chi‐Fai Ng, Hayley C. Whitaker, Yongwei Yu, Hongwei Zhang, Elizabeth Bancroft, Daniel M. Berney, Niedzica Camacho, Cathy Corbishley, Tokhir Dadaev, Nening M. Dennis, Tim Dudderidge, Sandra E. Edwards, Cyril Fisher, Jilur Ghori, Vincent J. Gnanapragasam, Christopher Greenman, Steve Hawkins, Steven Hazell, Will Howat, Katalin Karászi, Jonathan Kay, Zsofia Kote‐Jarai, Bárbara Kremeyer, Pardeep Kumar, Adam Lambert, Daniel Leongamornlert, Naomi Livni, Hayley J. Luxton, Lucy Matthews, Erik Mayer, Susan Merson, David Nicol, Christopher Ogden, Sarah O’Meara, Gill Pelvender, Nimish Shah, Simon Tavaré, Sarah Thomas, Alan Thompson, Clare Verrill, Anne Y. Warren, Jorge Zamora, Ultan McDermott, G. Steven Bova, Andrea L. Richardson, Adrienne M. Flanagan, Michael R. Stratton, Peter J. Campbell

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.

Bibliographic record

VenueNature Communications · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsHospital for Sick Children
FundersMedical Research CouncilUniversity College London Hospitals NHS Foundation TrustPublic Health EnglandRosetrees TrustNational Institute for Health and Care ResearchNational Institute for Health Research Health Protection Research UnitWellcome TrustFrancis Crick InstituteNewcastle UniversityCancer Research UK
KeywordsIonizing radiationBiologySomatic cellContext (archaeology)CarcinogenGeneticsGenomeGermline mutationMutationDNA damageCancer researchComputational biologyDNAGenePhysicsIrradiation

Abstract

fetched live from OpenAlex

Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1-100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.540
Threshold uncertainty score0.186

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 head0.010
GPT teacher head0.271
Teacher spread0.260 · 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