Browsing by Author "Clyde, MA"

Now showing 1 - 8 of 8
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    Bayesian model averaging: A tutorial - Comment
    (STATISTICAL SCIENCE, 1999-11) Clyde, MA
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    BAYESIAN MODEL SEARCH AND MULTILEVEL INFERENCE FOR SNP ASSOCIATION STUDIES.
    (Ann Appl Stat, 2010-09-01) Wilson, MA; Iversen, ES; Clyde, MA; Schmidler, SC; Schildkraut, JM
    Technological advances in genotyping have given rise to hypothesis-based association studies of increasing scope. As a result, the scientific hypotheses addressed by these studies have become more complex and more difficult to address using existing analytic methodologies. Obstacles to analysis include inference in the face of multiple comparisons, complications arising from correlations among the SNPs (single nucleotide polymorphisms), choice of their genetic parametrization and missing data. In this paper we present an efficient Bayesian model search strategy that searches over the space of genetic markers and their genetic parametrization. The resulting method for Multilevel Inference of SNP Associations, MISA, allows computation of multilevel posterior probabilities and Bayes factors at the global, gene and SNP level, with the prior distribution on SNP inclusion in the model providing an intrinsic multiplicity correction. We use simulated data sets to characterize MISA's statistical power, and show that MISA has higher power to detect association than standard procedures. Using data from the North Carolina Ovarian Cancer Study (NCOCS), MISA identifies variants that were not identified by standard methods and have been externally "validated" in independent studies. We examine sensitivity of the NCOCS results to prior choice and method for imputing missing data. MISA is available in an R package on CRAN.
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    Bayesian nonparametric models for peak identification in maldi-tof mass spectroscopy
    (Annals of Applied Statistics, 2011-06-01) House, LL; Clyde, MA; Wolpert, RL
    We present a novel nonparametric Bayesian approach based on Lévy Adaptive Regression Kernels (LARK) to model spectral data arising from MALDI-TOF (Matrix Assisted Laser Desorption Ionization Time-of-Flight) mass spectrometry. This model-based approach provides identification and quantification of proteins through model parameters that are directly interpretable as the number of proteins, mass and abundance of proteins and peak resolution, while having the ability to adapt to unknown smoothness as in wavelet based methods. Informative prior distributions on resolution are key to distinguishing true peaks from background noise and resolving broad peaks into individual peaks for multiple protein species. Posterior distributions are obtained using a reversible jump Markov chain Monte Carlo algorithm and provide inference about the number of peaks (proteins), their masses and abundance. We show through simulation studies that the procedure has desirable true-positive and false-discovery rates. Finally, we illustrate the method on five example spectra: a blank spectrum, a spectrum with only the matrix of a low-molecular-weight substance used to embed target proteins, a spectrum with known proteins, and a single spectrum and average of ten spectra from an individual lung cancer patient. © 2013 Institute of Mathematical Statistics.
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    Finite population estimators in stochastic search variable selection
    (BIOMETRIKA, 2012-12) Clyde, MA; Ghosh, J
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    Functional annotation signatures of disease susceptibility loci improve SNP association analysis.
    (BMC Genomics, 2014-05-24) Iversen, ES; Lipton, G; Clyde, MA; Monteiro, ANA
    BACKGROUND: Genetic association studies are conducted to discover genetic loci that contribute to an inherited trait, identify the variants behind these associations and ascertain their functional role in determining the phenotype. To date, functional annotations of the genetic variants have rarely played more than an indirect role in assessing evidence for association. Here, we demonstrate how these data can be systematically integrated into an association study's analysis plan. RESULTS: We developed a Bayesian statistical model for the prior probability of phenotype-genotype association that incorporates data from past association studies and publicly available functional annotation data regarding the susceptibility variants under study. The model takes the form of a binary regression of association status on a set of annotation variables whose coefficients were estimated through an analysis of associated SNPs in the GWAS Catalog (GC). The functional predictors examined included measures that have been demonstrated to correlate with the association status of SNPs in the GC and some whose utility in this regard is speculative: summaries of the UCSC Human Genome Browser ENCODE super-track data, dbSNP function class, sequence conservation summaries, proximity to genomic variants in the Database of Genomic Variants and known regulatory elements in the Open Regulatory Annotation database, PolyPhen-2 probabilities and RegulomeDB categories. Because we expected that only a fraction of the annotations would contribute to predicting association, we employed a penalized likelihood method to reduce the impact of non-informative predictors and evaluated the model's ability to predict GC SNPs not used to construct the model. We show that the functional data alone are predictive of a SNP's presence in the GC. Further, using data from a genome-wide study of ovarian cancer, we demonstrate that their use as prior data when testing for association is practical at the genome-wide scale and improves power to detect associations. CONCLUSIONS: We show how diverse functional annotations can be efficiently combined to create 'functional signatures' that predict the a priori odds of a variant's association to a trait and how these signatures can be integrated into a standard genome-wide-scale association analysis, resulting in improved power to detect truly associated variants.
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    Lossless online Bayesian bagging
    (JOURNAL OF MACHINE LEARNING RESEARCH, 2004-02) Lee, HKH; Clyde, MA
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    Mixtures of g-priors in Generalized Linear Models
    (2015) Li, Y; Clyde, MA
    Mixtures of Zellner's g-priors have been studied extensively in linear models and have been shown to have numerous desirable properties for Bayesian variable selection and model averaging. Several extensions of g-priors to Generalized Linear Models (GLMs) have been proposed in the literature; however, the choice of prior distribution of g and resulting properties for inference have received considerably less attention. In this paper, we extend mixtures of g-priors to GLMs by assigning the truncated Compound Confluent Hypergeometric (tCCH) distribution to 1/(1+g) and illustrate how this prior distribution encompasses several special cases of mixtures of g-priors in the literature, such as the Hyper-g, truncated Gamma, Beta-prime, and the Robust prior. Under an integrated Laplace approximation to the likelihood, the posterior distribution of 1/(1+g) is in turn a tCCH distribution, and approximate marginal likelihoods are thus available analytically. We discuss the local geometric properties of the g-prior in GLMs and show that specific choices of the hyper-parameters satisfy the various desiderata for model selection proposed by Bayarri et al, such as asymptotic model selection consistency, information consistency, intrinsic consistency, and measurement invariance. We also illustrate inference using these priors and contrast them to others in the literature via simulation and real examples.
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    Stochastic expansions using continuous dictionaries: Lévy adaptive regression kernels
    (Annals of Statistics, 2011-08-01) Wolpert, RL; Clyde, MA; Tu, C
    This article describes a new class of prior distributions for nonparametric function estimation. The unknown function is modeled as a limit of weighted sums of kernels or generator functions indexed by continuous parameters that control local and global features such as their translation, dilation, modulation and shape. Lévy random fields and their stochastic integrals are employed to induce prior distributions for the unknown functions or, equivalently, for the number of kernels and for the parameters governing their features. Scaling, shape, and other features of the generating functions are location-specific to allow quite different function properties in different parts of the space, as with wavelet bases and other methods employing overcomplete dictionaries. We provide conditions under which the stochastic expansions converge in specified Besov or Sobolev norms. Under a Gaussian error model, this may be viewed as a sparse regression problem, with regularization induced via the Lévy random field prior distribution. Posterior inference for the unknown functions is based on a reversible jump Markov chain Monte Carlo algorithm. We compare the Lévy Adaptive Regression Kernel (LARK) method to wavelet-based methods using some of the standard test functions, and illustrate its flexibility and adaptability in nonstationary applications. © Institute of Mathematical Statistics, 2011.