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Record W4403381371 · doi:10.1016/j.xgen.2024.100674

Long-read sequencing of an advanced cancer cohort resolves rearrangements, unravels haplotypes, and reveals methylation landscapes

2024· article· en· W4403381371 on OpenAlexafffund
Kieran O’Neill, Erin Pleasance, Jeremy Fan, Vahid Akbari, Glenn Chang, Katherine Dixon, Veronika Csizmók, Signe MacLennan, Vanessa Porter, Andrew Galbraith, Cameron J. Grisdale, Luka Culibrk, John H. Dupuis, Richard Corbett, James Hopkins, Reanne Bowlby, Pawan Pandoh, Duane E. Smailus, Dean Cheng, Tina Wong, Connor Frey, Yaoqing Shen, Eleanor Lewis, Luis F. Paulin, Fritz J. Sedlazeck, Jessica Nelson, Eric Chuah, Karen Mungall, Richard A. Moore, Robin Coope, Andrew J. Mungall, Melissa K. McConechy, Laura M. Williamson, Kasmintan A. Schrader, Stephen Yip, Marco A. Marra, Janessa Laskin, Steven J.M. Jones

Bibliographic record

VenueCell Genomics · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsBC Cancer AgencyUniversity of British ColumbiaCanada's Michael Smith Genome Sciences Centre
FundersBritish Columbia Knowledge Development FundNational Institutes of HealthBC Cancer FoundationTerry Fox FoundationGenome British ColumbiaTerry Fox Research InstituteCanada Foundation for InnovationCanadian Cancer Society Research InstituteCanadian Institutes of Health ResearchGenome Canada
KeywordsHaplotypeDNA methylationComputational biologyBiologyGeneticsMethylationCohortCancerEvolutionary biologyDNA sequencingGeneBioinformaticsMedicineGenotypeInternal medicine

Abstract

fetched live from OpenAlex

The Long-Read Personalized OncoGenomics (POG) dataset comprises a cohort of 189 patient tumors and 41 matched normal samples sequenced using the Oxford Nanopore Technologies PromethION platform. This dataset from the POG program and the Marathon of Hope Cancer Centres Network includes DNA and RNA short-read sequence data, analytics, and clinical information. We show the potential of long-read sequencing for resolving complex cancer-related structural variants, viral integrations, and extrachromosomal circular DNA. Long-range phasing facilitates the discovery of allelically differentially methylated regions (aDMRs) and allele-specific expression, including recurrent aDMRs in the cancer genes RET and CDKN2A. Germline promoter methylation in MLH1 can be directly observed in Lynch syndrome. Promoter methylation in BRCA1 and RAD51C is a likely driver behind homologous recombination deficiency where no coding driver mutation was found. This dataset demonstrates applications for long-read sequencing in precision medicine and is available as a resource for developing analytical approaches using this technology.

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)0.001
metaresearch head score (Gemma)0.002
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: Observational
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.006
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.002

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 head0.012
GPT teacher head0.271
Teacher spread0.259 · 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

Citations30
Published2024
Admission routes2
Has abstractyes

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