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Record W4312102322 · doi:10.21203/rs.3.rs-2394107/v1

Insights for precision healthcare from the 100,000 Genomes Cancer Programme

2022· preprint· en· W4312102322 on OpenAlexaff
Nirupa Murugaesu, Alona Sosinsky, John C. Ambrose, William Cross, Clare Turnbull, Shirley Henderson, Jennifer Jones, Angela Hamblin, Prabhu Arumugam, G. C. Chan, Daniel Chubb, Boris Noyvert, Jonathan Mitchell, Susan Walker, Katy Bowman, Dorota Pasko, M. B. Pereira, Nadezda Volkova, Antonio Rueda-Martin, Daniel Perez Gil, Javier Ferreiros, J. Pullinger, Afshan Siddiq, Tala Zainy, Tasnim Choudhury, Augusto Rendon, Tom Fowler, Sandra Hing, Zandra C. Deans, Genomics England Research Consortium, Sue Hill, Mark J. Caulfield

Bibliographic record

VenueResearch Square · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsInstitute of Cancer Research
FundersMedical Research CouncilCambridge University HospitalsUniversity of OxfordUniversity College LondonImperial College LondonNational Institute for Health and Care ResearchOxford University Hospitals NHS Foundation TrustCancer Research UKUniversity of CambridgeDepartment of Health and Social CareWellcome Trust
KeywordsHealth careCancerGenomeBiologyComputational biologyPolitical scienceGeneticsGene

Abstract

fetched live from OpenAlex

Abstract The Cancer Programme of the 100,000 Genomes Project was a transformational UK government initiative that aimed to bring whole genome sequencing (WGS) to cancer patients and evaluate the opportunities for precision cancer care. Genomics England, in partnership with NHS England, generated whole genome analyses for 13,880 solid tumours across 33 different cancer types, and genomic data were linked with real-world health data within a secure national research environment. Here, we report the overall findings of the programme, focusing on clinical actionability and potential wider clinical significance. We found variation between cancer types in the incidence of somatic mutations of different types in genes currently recommended for standard-of-care testing. For example, 94% of glioblastoma multiforme cases had small variants and 54% had copy number aberrations (CNAs) in at least one gene recommended for clinical testing, whereas sarcoma was found to have the highest proportion of actionable structural variants (13%). We confirmed the importance of utilising pan- genomic markers, such as mutational signatures, with 51% of high grade serous ovarian cancer cases showing homologous recombination deficiency, 13% of which were associated with pathogenic germline variants, indicating the value of combined somatic and germline analyses. We also observed a significant co-occurrence of somatic small variants and CNAs in several known oncogenes including EGFR, GNAS, BRAF, and KRAS. Our findings demonstrate the value of combining genomic testing with real world clinical and treatment data to inform clinical recommendations for genomic testing in cancer, to enable survival analysis and improve understanding of the long-term effects of clinical cancer genomics on patient outcomes.

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)0.030
metaresearch head score (Gemma)0.063
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.030
Threshold uncertainty score0.158

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0300.063
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.003
Science and technology studies0.0010.002
Scholarly communication0.0060.004
Open science0.0020.007
Research integrity0.0060.008
Insufficient payload (model declined to judge)0.0140.003

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 head0.091
GPT teacher head0.419
Teacher spread0.328 · 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 designNot applicable
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

Citations1
Published2022
Admission routes1
Has abstractyes

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