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Record W3186172985 · doi:10.1101/2021.07.19.452658

Absolute copy number fitting from shallow whole genome sequencing data

2021· preprint· en· W3186172985 on OpenAlexfundno aff
Carolin M. Sauer, Matthew Eldridge, Maria Vias, James Hall, Samantha E. Boyle, Geoff Macintyre, Thomas Bradley, Florian Markowetz, James D. Brenton

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsnot available
FundersNIHR Cambridge Biomedical Research CentreCancer Research UK Cambridge Institute, University of CambridgeFonds de Recherche du Québec - SantéNational Institute for Health and Care ResearchCancer Research UK
KeywordsCopy-number variationGenomeWhole genome sequencingComputational biologyCancer cell linesDNA sequencingVisualizationCancerComputer scienceBiologyGeneticsDNAData miningGeneCancer cell

Abstract

fetched live from OpenAlex

Abstract Low-coverage or shallow whole genome sequencing (sWGS) approaches can efficiently detect somatic copy number aberrations (SCNAs) at low cost. This is clinically important for many cancers, in particular cancers with severe chromosomal instability (CIN) that frequently lack actionable point mutations and are characterised by poor disease outcome. Absolute copy number (ACN), measured in DNA copies per cancer cell, is required for meaningful comparisons between copy number states, but is challenging to estimate and in practice often requires manual curation. Using a total of 60 cancer cell lines, 148 patient-derived xenograft (PDX) and 142 clinical tissue samples, we evaluate the performance of available tools for obtaining ACN from sWGS. We provide a validated and refined tool called Rascal ( r elative to a bsolute copy number scal ing) that provides improved fitting algorithms and enables interactive visualisation of copy number profiles. These approaches are highly applicable to both pre-clinical and translational research studies on SCNA-driven cancers and provide more robust ACN fits from sWGS data than currently available tools.

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)0.003
metaresearch head score (Gemma)0.010
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.007
Threshold uncertainty score0.023

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.010
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.003
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0070.003

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 head0.023
GPT teacher head0.241
Teacher spread0.218 · 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 designSimulation or modeling
Domainnot available
GenreMethods

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

Citations24
Published2021
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicCancer Genomics and DiagnosticsFrench-language works237,207