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Record W2892566153 · doi:10.1038/s41467-018-06354-3

Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma

2018· article· en· W2892566153 on OpenAlexafffund
Sarah E. Arthur, Aixiang Jiang, Bruno M. Grande, Miguel Alcaide, Razvan Cojocaru, Christopher Rushton, Anja Mottok, Laura K. Hilton, Prince Kumar Lat, Eric Y. Stutheit-Zhao, Luka Culibrk, Daisuke Ennishi, Selin Jessa, Lauren C. Chong, Nicole Thomas, Prasath Pararajalingam, Barbara Meissner, Merrill Boyle, Jordan Davidson, Kevin Bushell, Daniel Lai, Pedro Farinha, Graham W. Slack, Gregg B. Morin, Sohrab P. Shah, Dipankar Sen, Steven J.M. Jones, Andrew J. Mungall, Randy D. Gascoyne, Timothy E. Audas, Peter J. Unrau, Marco A. Marra, Joseph M. Connors, Christian Steidl, David W. Scott, Ryan D. Morin

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsUniversity of British ColumbiaOccupational Cancer Research CentreCanada's Michael Smith Genome Sciences CentreSimon Fraser University
FundersDeutsche KrebshilfeTerry Fox Research InstituteGenome British ColumbiaMichael Smith Health Research BCCanada Research ChairsInstituto Carlos Slim de la SaludGovernment of CanadaCanadian Institutes of Health ResearchGenome Canada
KeywordsSomatic cellGenomeDiffuse large B-cell lymphomaComputational biologyBiologyGeneticsLymphomaGeneImmunology

Abstract

fetched live from OpenAlex

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3' UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NF-κB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor protein IIB), primarily in the germinal centre B-cell (GCB) subgroup, correlate with poor patient outcomes suggestive of a novel oncogene. These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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: Empirical · Consensus signal: Empirical
Teacher disagreement score0.761
Threshold uncertainty score0.419

Codex and Gemma teacher scores by category

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

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 head0.007
GPT teacher head0.251
Teacher spread0.243 · 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 teacher head, 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

Citations148
Published2018
Admission routes2
Has abstractyes

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