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Record W3113006061 · doi:10.1038/s41587-020-0719-5

Fully phased human genome assembly without parental data using single-cell strand sequencing and long reads

2020· article· en· W3113006061 on OpenAlexaff
David Porubskỳ, Peter Ebert, Peter A. Audano, Mitchell R. Vollger, William T. Harvey, Pierre Marijon, Jana Ebler, Katherine M. Munson, Melanie Sorensen, Arvis Sulovari, Marina Haukness, Maryam Ghareghani, Peter M. Lansdorp, Benedict Paten, Scott E. Devine, Ashley D. Sanders, Charles Lee, Mark Chaisson, Jan O. Korbel, Evan E. Eichler, Tobias Marschall

Bibliographic record

VenueNature Biotechnology · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Phylogenetic Studies
Canadian institutionsUniversity of British ColumbiaBC Cancer Agency
FundersNational Cancer InstituteNational Institutes of HealthGerman Network for Bioinformatics InfrastructureEwha Womans UniversityNational Human Genome Research InstituteBundesministerium für Bildung und ForschungU.S. National Library of MedicineDeutsche ForschungsgemeinschaftHoward Hughes Medical Institute
KeywordsContigSequence assemblyGenomeIndelBiologyNanopore sequencingHuman genomeGeneticsHaplotypeComputational biologyReference genomeHybrid genome assemblyDNA sequencingStructural variationGeneSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Abstract Human genomes are typically assembled as consensus sequences that lack information on parental haplotypes. Here we describe a reference-free workflow for diploid de novo genome assembly that combines the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing 1,2 with continuous long-read or high-fidelity 3 sequencing data. Employing this strategy, we produced a completely phased de novo genome assembly for each haplotype of an individual of Puerto Rican descent (HG00733) in the absence of parental data. The assemblies are accurate (quality value > 40) and highly contiguous (contig N50 > 23 Mbp) with low switch error rates (0.17%), providing fully phased single-nucleotide variants, indels and structural variants. A comparison of Oxford Nanopore Technologies and Pacific Biosciences phased assemblies identified 154 regions that are preferential sites of contig breaks, irrespective of sequencing technology or phasing algorithms.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.002

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 head0.042
GPT teacher head0.281
Teacher spread0.240 · 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
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

Citations225
Published2020
Admission routes1
Has abstractyes

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