Literature DB >> 32542104

VARIABLE PRIORITIZATION IN NONLINEAR BLACK BOX METHODS: A GENETIC ASSOCIATION CASE STUDY1.

Lorin Crawford1, Seth R Flaxman2, Daniel E Runcie3, Mike West4.   

Abstract

The central aim in this paper is to address variable selection questions in nonlinear and nonparametric regression. Motivated by statistical genetics, where nonlinear interactions are of particular interest, we introduce a novel and interpretable way to summarize the relative importance of predictor variables. Methodologically, we develop the "RelATive cEntrality" (RATE) measure to prioritize candidate genetic variants that are not just marginally important, but whose associations also stem from significant covarying relationships with other variants in the data. We illustrate RATE through Bayesian Gaussian process regression, but the methodological innovations apply to other "black box" methods. It is known that nonlinear models often exhibit greater predictive accuracy than linear models, particularly for phenotypes generated by complex genetic architectures. With detailed simulations and two real data association mapping studies, we show that applying RATE enables an explanation for this improved performance.

Entities:  

Keywords:  Gaussian processes; Nonlinear regression; centrality measures; genome-wide association studies; statistical genetics; variable prioritization

Year:  2019        PMID: 32542104      PMCID: PMC7295151          DOI: 10.1214/18-aoas1222

Source DB:  PubMed          Journal:  Ann Appl Stat        ISSN: 1932-6157            Impact factor:   2.083


  59 in total

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3.  R/qtlbim: QTL with Bayesian Interval Mapping in experimental crosses.

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Journal:  Bioinformatics       Date:  2007-01-19       Impact factor: 6.937

Review 4.  Bayesian statistical methods for genetic association studies.

Authors:  Matthew Stephens; David J Balding
Journal:  Nat Rev Genet       Date:  2009-10       Impact factor: 53.242

5.  Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth.

Authors:  G A Brockmann; C S Haley; U Renne; S A Knott; M Schwerin
Journal:  Genetics       Date:  1998-09       Impact factor: 4.562

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Journal:  Cell       Date:  1996-04-19       Impact factor: 41.582

8.  Ultrafast genome-wide scan for SNP-SNP interactions in common complex disease.

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Journal:  Genome Res       Date:  2012-07-05       Impact factor: 9.043

9.  Non-parametric genetic prediction of complex traits with latent Dirichlet process regression models.

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Journal:  Nat Commun       Date:  2017-09-06       Impact factor: 14.919

10.  Evaluation of the lasso and the elastic net in genome-wide association studies.

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Journal:  Front Genet       Date:  2013-12-04       Impact factor: 4.599

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  2 in total

1.  Multi-scale inference of genetic trait architecture using biologically annotated neural networks.

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Journal:  PLoS Genet       Date:  2021-08-19       Impact factor: 5.917

2.  A topological data analytic approach for discovering biophysical signatures in protein dynamics.

Authors:  Wai Shing Tang; Gabriel Monteiro da Silva; Henry Kirveslahti; Erin Skeens; Bibo Feng; Timothy Sudijono; Kevin K Yang; Sayan Mukherjee; Brenda Rubenstein; Lorin Crawford
Journal:  PLoS Comput Biol       Date:  2022-05-02       Impact factor: 4.779

  2 in total

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