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Record W3040343536 · doi:10.1038/s41467-020-17095-7

IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms

2020· article· en· W3040343536 on OpenAlexaff
Ferran Nadeu, Rut Mas-de-les-Valls, Alba Navarro, Romina Royo, Silvia Martín, Neus Villamor, Helena Suárez-Cisneros, Rosó Marés, Junyan Lu, Anna Enjuanes, Alfredo Rivas‐Delgado, Marta Aymerich, Tycho Baumann, Dolors Colomer, Julio Delgado, Ryan D. Morin, Thorsten Zenz, Xosé S. Puente, Peter J. Campbell, Sı́lvia Beà, Francesco Maura, Elı́as Campo

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsCanada's Michael Smith Genome Sciences CentreSimon Fraser University
FundersInstituto de Salud Carlos IIIHeidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-GemeinschaftFundación Bancaria Caixa d'Estalvis i Pensions de BarcelonaInstitució Catalana de Recerca i Estudis AvançatsNational Cancer InstituteGeneralitat de CatalunyaMinisterio de Economía y CompetitividadCentres de Recerca de CatalunyaEuropean Regional Development FundDeutsches KrebsforschungszentrumMemorial Sloan-Kettering Cancer Center
KeywordsSanger sequencingBiologyGenomeGeneChromosomal translocationGeneticsDNA sequencingFluorescence in situ hybridizationComputational biologyImmunoglobulin heavy chainChromosome

Abstract

fetched live from OpenAlex

Immunoglobulin (Ig) gene rearrangements and oncogenic translocations are routinely assessed during the characterization of B cell neoplasms and stratification of patients with distinct clinical and biological features, with the assessment done using Sanger sequencing, targeted next-generation sequencing, or fluorescence in situ hybridization (FISH). Currently, a complete Ig characterization cannot be extracted from whole-genome sequencing (WGS) data due to the inherent complexity of the Ig loci. Here, we introduce IgCaller, an algorithm designed to fully characterize Ig gene rearrangements and oncogenic translocations from short-read WGS data. Using a cohort of 404 patients comprising different subtypes of B cell neoplasms, we demonstrate that IgCaller identifies both heavy and light chain rearrangements to provide additional information on their functionality, somatic mutational status, class switch recombination, and oncogenic Ig translocations. Our data thus support IgCaller to be a reliable alternative to Sanger sequencing and FISH for studying the genetic properties of the Ig loci.

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)0.006
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: Methods
Teacher disagreement score0.006
Threshold uncertainty score0.021

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.006
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0010.000
Scholarly communication0.0020.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0060.002

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 head0.063
GPT teacher head0.331
Teacher spread0.269 · 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

Citations40
Published2020
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicChronic Lymphocytic Leukemia ResearchFrench-language works237,207