J Am Med Inform Assoc - Stochastic model search with binary outcomes for genome-wide association studies.

Tópicos

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Resumo

JECTIVE: The spread of case-control genome-wide association studies (GWASs) has stimulated the development of new variable selection methods and predictive models. We introduce a novel Bayesian model search algorithm, Binary Outcome Stochastic Search (BOSS), which addresses the model selection problem when the number of predictors far exceeds the number of binary responses.MATERIALS AND METHODS: Our method is based on a latent variable model that links the observed outcomes to the underlying genetic variables. A Markov Chain Monte Carlo approach is used for model search and to evaluate the posterior probability of each predictor.RESULTS: BOSS is compared with three established methods (stepwise regression, logistic lasso, and elastic net) in a simulated benchmark. Two real case studies are also investigated: a GWAS on the genetic bases of longevity, and the type 2 diabetes study from the Wellcome Trust Case Control Consortium. Simulations show that BOSS achieves higher precisions than the reference methods while preserving good recall rates. In both experimental studies, BOSS successfully detects genetic polymorphisms previously reported to be associated with the analyzed phenotypes.DISCUSSION: BOSS outperforms the other methods in terms of F-measure on simulated data. In the two real studies, BOSS successfully detects biologically relevant features, some of which are missed by univariate analysis and the three reference techniques.CONCLUSION: The proposed algorithm is an advance in the methodology for model selection with a large number of features. Our simulated and experimental results showed that BOSS proves effective in detecting relevant markers while providing a parsimonious model.

Resumo Limpo

jectiv spread casecontrol genomewid associ studi gwass stimul develop new variabl select method predict model introduc novel bayesian model search algorithm binari outcom stochast search boss address model select problem number predictor far exceed number binari responsesmateri method method base latent variabl model link observ outcom under genet variabl markov chain mont carlo approach use model search evalu posterior probabl predictorresult boss compar three establish method stepwis regress logist lasso elast net simul benchmark two real case studi also investig gwas genet base longev type diabet studi wellcom trust case control consortium simul show boss achiev higher precis refer method preserv good recal rate experiment studi boss success detect genet polymorph previous report associ analyz phenotypesdiscuss boss outperform method term fmeasur simul data two real studi boss success detect biolog relev featur miss univari analysi three refer techniquesconclus propos algorithm advanc methodolog model select larg number featur simul experiment result show boss prove effect detect relev marker provid parsimoni model

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