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Record W2950522632 · doi:10.1093/bioinformatics/btz518

Bayesian GWAS with Structured and Non-Local Priors

2019· article· en· W2950522632 on OpenAlexfundno aff
Adam Kaplan, Eric F. Lock, Mark Fiecas

Bibliographic record

VenueBioinformatics · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthGenentechTakeda Pharmaceutical CompanyIXICONational Institute of General Medical SciencesH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationPfizerBiogenBioClinicaRocheUniversity of Southern CaliforniaF. Hoffmann-La RocheNovartis Pharmaceuticals CorporationU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbMerckAlzheimer's AssociationFoundation for the National Institutes of HealthAlzheimer's Disease Neuroimaging InitiativeMeso Scale Diagnostics
KeywordsPrior probabilityBayesian probabilityComputer scienceGenome-wide association studyStatistical powerCovariateMachine learningArtificial intelligenceStatisticsMathematicsSingle-nucleotide polymorphismBiology

Abstract

fetched live from OpenAlex

MOTIVATION: The flexibility of a Bayesian framework is promising for GWAS, but current approaches can benefit from more informative prior models. We introduce a novel Bayesian approach to GWAS, called Structured and Non-Local Priors (SNLPs) GWAS, that improves over existing methods in two important ways. First, we describe a model that allows for a marker's gene-parent membership and other characteristics to influence its probability of association with an outcome. Second, we describe a non-local alternative model for differential minor allele rates at each marker, in which the null and alternative hypotheses have no common support. RESULTS: We employ a non-parametric model that allows for clustering of the genes in tandem with a regression model for marker-level covariates, and demonstrate how incorporating these additional characteristics can improve power. We further demonstrate that our non-local alternative model gives symmetric rates of convergence for the null and alternative hypotheses, whereas commonly used local alternative models have asymptotic rates that favor the alternative hypothesis over the null. We demonstrate the robustness and flexibility of our structured and non-local model for different data generating scenarios and signal-to-noise ratios. We apply our Bayesian GWAS method to single nucleotide polymorphisms data collected from a pool of Alzheimer's disease and cognitively normal patients from the Alzheimer's Database Neuroimaging Initiative. AVAILABILITY AND IMPLEMENTATION: R code to perform the SNLPs method is available at https://github.com/lockEF/BayesianScreening.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.093
Threshold uncertainty score0.331

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 head0.004
GPT teacher head0.212
Teacher spread0.208 · 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 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

Citations2
Published2019
Admission routes1
Has abstractyes

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