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Record W4403090011 · doi:10.1101/2024.10.02.616333

The Platinum Pedigree: A long-read benchmark for genetic variants

2024· preprint· en· W4403090011 on OpenAlexaff
Zev Kronenberg, C. Nolan, Tom Mokveld, William J. Rowell, S. Y. Lee, Egor Dolzhenko, Pi-Chuan Chang, James Holt, Christopher T. Saunders, Nathan D. Olson, Sean McGee, Andrea Guarracino, Nidhi Koundinya, William T. Harvey, W. Scott Watkins, Katherine M. Munson, Kendra Hoekzema, Khi Pin Chua, Cairbre Fanslow, Christine Lambert, Harriet Dashnow, Erik Garrison, Joshua D. Smith, Peter M. Lansdorp, Justin M. Zook, Andrew Carroll, Lynn B. Jorde, Deborah W. Neklason, Aaron R. Quinlan, Evan E. Eichler, Michael A. Eberle

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsBC Cancer Agency
FundersNational Institute of Standards and TechnologyNational Institutes of Health
KeywordsBenchmark (surveying)PlatinumComputer scienceGeneticsBiologyComputational biologyGeographyBiochemistryCartography

Abstract

fetched live from OpenAlex

Recent advances in genome sequencing have improved variant calling in complex regions of the human genome. However, it is difficult to quantify variant calling performance since existing standards often focus on specificity, neglecting completeness in difficult to analyze regions. To create a more comprehensive truth set, we used Mendelian inheritance in a large pedigree (CEPH-1463) to filter variants across Illumina, PacBio high-fidelity (HiFi), and Oxford Nanopore Technologies platforms. This generated a variant map with over 4.7 million single-nucleotide variants, 767,795 indels, 537,486 tandem repeats, and 24,315 structural variants, covering 2.77 Gb of the GRCh38 genome. This work adds ~200 Mb of high-confidence regions, including 8% more small variants, and introduces the first tandem repeat and structural variant truth sets for NA12878. As an example of the value of this improved benchmark, we retrained DeepVariant using this data to reduce genotyping errors by ~34%.

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)0.006
metaresearch head score (Gemma)0.025
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.011
Threshold uncertainty score0.030

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0060.025
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.003
Science and technology studies0.0010.001
Scholarly communication0.0020.002
Open science0.0030.002
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0070.004

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 head0.008
GPT teacher head0.222
Teacher spread0.213 · 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 designBench or experimental
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

Citations6
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicGenomics and Rare DiseasesFrench-language works237,207