MétaCan
Menu
Back to cohort
Record W4404051442 · doi:10.1101/2024.10.29.620968

Robust fine-mapping in the presence of linkage disequilibrium mismatch

2024· preprint· en· W4404051442 on OpenAlexaff
Wenmin Zhang, Tianyuan Lu, Robert Sladek, Josée Dupuis, Guillaume Lettre

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldComputer Science
TopicOptimization and Variational Analysis
Canadian institutionsMcGill UniversityMontreal Heart Institute
Fundersnot available
KeywordsLinkage disequilibriumDisequilibriumLinkage (software)Computational biologyComputer scienceGeneticsBiologyMedicineHaplotypeGenotype

Abstract

fetched live from OpenAlex

Abstract Fine-mapping methods based on summary statistics from genome-wide association studies (GWAS) and linkage disequilibrium (LD) information are widely used to identify potential causal variants. However, LD mismatch between the external LD reference panel and the GWAS population is common and can lead to compromised accuracy of fine-mapping. We developed RSparsePro, a probabilistic graphical model with an efficient variational inference algorithm, to perform robust fine-mapping in the presence of LD mismatch. In simulation studies with a varying degree of LD mismatch, RSparsePro identified credible sets with a consistently higher power and coverage than SuSiE. In fine-mapping cis-protein quantitative trait loci, RSparsePro identified credible sets with a consistently higher enrichment of variants with functional impacts and cross-study replication rates. In fine-mapping risk loci for low-density lipoprotein cholesterol in ancestry-specific GWAS, RSparsePro identified biologically relevant variants in drug target genes and implicated potential regulatory mechanisms. RSparsePro is openly available at https://github.com/zhwm/RSparsePro_LD .

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)0.012
metaresearch head score (Gemma)0.036
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.012
Threshold uncertainty score0.062

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0120.036
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0010.001
Science and technology studies0.0010.002
Scholarly communication0.0010.002
Open science0.0020.004
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.000

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 head0.023
GPT teacher head0.220
Teacher spread0.197 · 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 designSimulation or modeling
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

Citations7
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicOptimization and Variational AnalysisFrench-language works237,207