MétaCan
Menu
Back to cohort
Record W4281762473 · doi:10.1101/2022.06.04.22275962

Identification of gene fusions associated with amyotrophic lateral sclerosis

2022· preprint· en· W4281762473 on OpenAlexaff
Yogindra Raghav, Allison A. Dilliott, Tiziana Petrozziello, Spencer E. Kim, James D. Berry, Merit Cudkowicz, Khashayar Vakili, Ernest Fraenkel, Sali M.K. Farhan, Ghazaleh Sadri‐Vakili

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsMontreal Neurological Institute and HospitalMcGill University
FundersNew York Genome CenterTarget ALSTow FoundationALS Association
KeywordsAmyotrophic lateral sclerosisGeneBiologyFusion geneGeneticsDiseaseMedicinePathology

Abstract

fetched live from OpenAlex

Abstract Genetics is an import risk factor for amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease affecting motor neurons. Recent findings demonstrate that, in addition to specific genetic mutations, structural variants caused by genetic instability can also play a causative role in ALS. Genomic instability can lead to deletions, duplications, insertions, inversions, and translocations in the genome, and these changes can sometimes lead to fusion of distinct genes into a single transcript. While such gene fusion events have been studied extensively in cancer, they have not been thoroughly investigated in ALS. We leveraged bulk RNA-Seq data from human post-mortem samples to determine whether fusion events occur in ALS. We report for the first time the presence of gene fusion events in several brain regions as well as in spinal cord samples in ALS. Although most gene fusions were intra-chromosomal events between neighboring genes and present in both ALS and control samples, there was a significant increase in the number of unique gene fusion in ALS compared to controls. Lastly, we have identified specific gene fusions with a significant burden in ALS, that were absent from both control samples and known cancer gene fusion databases. Collectively, our findings reveal an enrichment of gene fusion in ALS and suggest that these events may be an additional genetic cause linked to ALS pathogenesis.

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)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.001

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 head0.054
GPT teacher head0.299
Teacher spread0.245 · 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 designObservational
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

Citations5
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuemedRxivSame topicAmyotrophic Lateral Sclerosis ResearchFrench-language works237,207