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A hybrid method of the sequential Monte Carlo and the Edgeworth expansion for computation of very small p-values in permutation tests.

ABSTRACT: Permutation tests are very useful when parametric assumptions are violated or distributions of test statistics are mathematically intractable. The major advantage of permutation tests is that the procedure is so general that it is applicable to most test statistics. The computational expense is, however, impractical in high-dimensional settings such as genomewide association studies. This study provides a comprehensive review of existing methods that can compute very small p-values efficiently. A common issue with existing methods is that they can only be applied to a specific test statistic. To fill in the knowledge gap, we propose a hybrid method of the sequential Monte Carlo and the Edgeworth expansion approximation for a studentized statistic, which is applicable to a variety of test statistics. The simulation results show that the proposed method performs better than competing methods. Furthermore, applications of the proposed method are demonstrated by statistical analysis on the genomewide association studies data from the Study of Addiction: Genetics and Environment (SAGE).

SUBMITTER: Yang JJ

PROVIDER: S-EPMC6360137 | biostudies-literature | 2019 Oct-Nov

REPOSITORIES: biostudies-literature

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A hybrid method of the sequential Monte Carlo and the Edgeworth expansion for computation of very small <i>p</i>-values in permutation tests.

Yang James J JJ Trucco Elisa M EM Buu Anne A

Statistical methods in medical research 20180803 10-11

Permutation tests are very useful when parametric assumptions are violated or distributions of test statistics are mathematically intractable. The major advantage of permutation tests is that the procedure is so general that it is applicable to most test statistics. The computational expense is, however, impractical in high-dimensional settings such as genomewide association studies. This study provides a comprehensive review of existing methods that can compute very small <i>p</i>-values effici ...[more]

PMID: 30073912

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Project description:High-throughput gene expression data are often obtained from pure or complex (heterogeneous) biological samples. In the latter case, data obtained are a mixture of different cell types and the heterogeneity imposes some difficulties in the analysis of such data. In order to make conclusions on gene expresssion data obtained from heterogeneous samples, methods such as microdissection and flow cytometry have been employed to physically separate the constituting cell types. However, these manual approaches are time consuming when measuring the responses of multiple cell types simultaneously. In addition, exposed samples, on many occasions, end up being contaminated with external perturbations and this may result in an altered yield of molecular content. In this paper, we model the heterogeneous gene expression data using a Bayesian framework, treating the cell type proportions and the cell-type specific expressions as the parameters of the model. Specifically, we present a novel sequential Monte Carlo (SMC) sampler for estimating the model parameters by approximating their posterior distributions with a set of weighted samples. The SMC framework is a robust and efficient approach where we construct a sequence of artificial target (posterior) distributions on spaces of increasing dimensions which admit the distributions of interest as marginals. The proposed algorithm is evaluated on simulated datasets and publicly available real datasets, including Affymetrix oligonucleotide arrays and national center for biotechnology information (NCBI) gene expression omnibus (GEO), with varying number of cell types. The results obtained on all datasets show a superior performance with an improved accuracy in the estimation of cell type proportions and the cell-type specific expressions, and in addition, more accurate identification of differentially expressed genes when compared to other widely known methods for blind decomposition of heterogeneous gene expression data such as Dsection and the nonnegative matrix factorization (NMF) algorithms. MATLAB implementation of the proposed SMC algorithm is available to download at https://github.com/moyanre/smcgenedeconv.git.

Dataset Information

A hybrid method of the sequential Monte Carlo and the Edgeworth expansion for computation of very small p-values in permutation tests.

Publications

A hybrid method of the sequential Monte Carlo and the Edgeworth expansion for computation of very small <i>p</i>-values in permutation tests.

Similar Datasets

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