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Record W2948704538 · doi:10.1371/journal.pgen.1008180

Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease

2019· article· en· W2948704538 on OpenAlexafffund
Carles Vilariño‐Güell, Alexander Zimprich, Filippo Martinelli Boneschi, Bruno Herculano, Zhe Wang, Fuencisla Matesanz, Elena Urcelay, Koen Vandenbroeck, Laura Leyva, Denis Gris, Charbel Massaad, Jacqueline A. Quandt, Anthony Traboulsee, Mary Joy Encarnacion, Cecily Q. Bernales, Jordan Follett, Irene M. Yee, Maria Criscuoli, Angela Deutschländer, Eva M. Reinthaler, Tobias Zrzavy, Elisabetta Mascia, Andrea Zauli, Federica Esposito, Antonio Alcina, Laura Espino‐Paisán, Jorge Mena, Alfredo Rodríguez Antigüedad, Patricia Urbaneja-Romero, Jesús Ortega-Pinazo, Weihong Song, A. Dessa Sadovnick

Post-publication record

NatureExpression of concern
ReasonConcerns/Issues about Data;Concerns/Issues about Results and/or Conclusions;Investigation by Journal/Publisher;Objections by Third Party;
Date10/11/2019 0:00
Flagged by OpenAlex?No. Retraction Watch records this, and OpenAlex does not flag it.

Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement; it reports them as false, which reads as “fine”.

Bibliographic record

VenuePLoS Genetics · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
Topicinterferon and immune responses
Canadian institutionsUniversité de SherbrookeUniversity of British Columbia
FundersInstitute of GeneticsInstituto de Salud Carlos IIICanadian Institutes of Health ResearchVancouver Coastal Health Research InstituteMinisterio de Economía y CompetitividadMinistero della SaluteRed Española de Esclerosis MúltipleMichael Smith Health Research BCCanada Research ChairsEuropean Regional Development FundVancouver Foundation
KeywordsBiologyExome sequencingMultiple sclerosisTREM2GeneticsNeurodegenerationExomeInflammasomeInflammationInnate immune systemMissense mutationGeneImmunologyImmune systemDiseaseMicrogliaMutationMedicine

Abstract

fetched live from OpenAlex

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.027
Threshold uncertainty score0.395

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 science0.0000.000
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 head0.068
GPT teacher head0.229
Teacher spread0.161 · 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

Citations80
Published2019
Admission routes2
Has abstractyes

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