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Record W4382198075 · doi:10.1101/2023.06.20.23291658

Identification of novel variants, genes and pathways potentially linked to Parkinson’s disease using machine learning

2023· preprint· en· W4382198075 on OpenAlexafffund
Eric Yu, Roxanne Larivière, Rhalena A. Thomas, Lang Liu, Konstantin Senkevich, Shady Rahayel, Jean‐François Trempe, Edward A. Fon, Ziv Gan‐Or

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicStudies on Chitinases and Chitosanases
Canadian institutionsUniversité de MontréalHôpital du Sacré-Cœur de MontréalMcGill UniversityMontreal Neurological Institute and Hospital
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchNational Institutes of HealthCanada First Research Excellence FundConsortium canadien en neurodégénérescence associée au vieillissementKillam TrustsMcGill UniversityCelgeneSanofiGlaxoSmithKlinePfizerNational Institute of Neurological Disorders and StrokeVerily Life SciencesBristol-Myers SquibbMichael J. Fox Foundation for Parkinson's ResearchFoundation for the National Institutes of Health
KeywordsGenome-wide association studyLRRK2GeneLocus (genetics)BiologyParkinson's diseaseGeneticsCandidate geneComputational biologyBiological pathwayEpigenomicsGenetic associationTranscriptomeSingle-nucleotide polymorphismDiseaseGene expressionMedicineMutationGenotype

Abstract

fetched live from OpenAlex

Abstract There are 78 loci associated with Parkinson’s disease (PD) in the most recent genome-wide association study (GWAS), yet the specific genes driving these associations are mostly unknown. Herein, we aimed to nominate the top candidate gene from each PD locus, and identify variants and pathways potentially involved in PD. We trained a machine learning model to predict PD-associated genes from GWAS loci using genomic, transcriptomic, and epigenomic data from brain tissues and dopaminergic neurons. We nominated candidate genes in each locus, identified novel pathways potentially involved in PD, such as the inositol phosphate biosynthetic pathway ( INPP5F , IP6K2 , ITPKB, PPIP5K2 ). Specific common coding variants in SPNS1 and MLX may be involved in PD, and burden tests of rare variants further support that CNIP3 , LSM7 , NUCKS1 and the polyol/inositol phosphate biosynthetic pathway are associated with PD. Functional studies are needed to further analyze the involvements of these genes and pathways in PD.

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 score0.815
Threshold uncertainty score0.988

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 science0.0000.001
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 head0.041
GPT teacher head0.277
Teacher spread0.236 · 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

Citations3
Published2023
Admission routes2
Has abstractyes

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