Douglas M. Bates

Bio: Douglas M. Bates is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Generalized linear mixed model & Random effects model. The author has an hindex of 36, co-authored 80 publications receiving 88022 citations. Previous affiliations of Douglas M. Bates include Kansas State University & University of Alberta.

Balancing Type I Error and Power in Linear Mixed Models

Abstract: Linear mixed-effects models have increasingly replaced mixed-model analyses of variance for statistical inference in factorial psycholinguistic experiments. Although LMMs have many advantages over ANOVA, like ANOVAs, setting them up for data analysis also requires some care. One simple option, when numerically possible, is to fit the full variance-covariance structure of random effects (the maximal model; Barr et al. 2013), presumably to keep Type I error down to the nominal alpha in the presence of random effects. Although it is true that fitting a model with only random intercepts may lead to higher Type I error, fitting a maximal model also has a cost: it can lead to a significant loss of power. We demonstrate this with simulations and suggest that for typical psychological and psycholinguistic data, higher power is achieved without inflating Type I error rate if a model selection criterion is used to select a random effect structure that is supported by the data.

Estimating the Multilevel Rasch Model: With the lme4 Package

Abstract: Traditional Rasch estimation of the item and student parameters via marginal maximum likelihood, joint maximum likelihood or conditional maximum likelihood, assume individuals in clustered settings are uncorrelated and items within a test that share a grouping structure are also uncorrelated. These assumptions are often violated, particularly in educational testing situations, in which students are grouped into classrooms and many test items share a common grouping structure, such as a content strand or a reading passage. Consequently, one possible approach is to explicitly recognize the clustered nature of the data and directly incorporate random effects to account for the various dependencies. This article demonstrates how the multilevel Rasch model can be estimated using the functions in R for mixed-effects models with crossed or partially crossed random effects. We demonstrate how to model the following hierarchical data structures: a) individuals clustered in similar settings (e.g., classrooms, schools), b) items nested within a particular group (such as a content strand or a reading passage), and c) how to estimate a teacher x content strand interaction.

Technical note: an R package for fitting generalized linear mixed models in animal breeding.

Abstract: Mixed models have been used extensively in quantitative genetics to study continuous and discrete traits. A standard quantitative genetic model proposes that the effects of levels of some random factor (e.g., sire) are correlated accordingly with their relationships. For this reason, routines for mixed models available in standard packages cannot be used for genetic analysis. The pedigreemm package of R was developed as an extension of the lme4 package, and allows mixed models with correlated random effects to be fitted for Gaussian, binary, and count responses. Following the method of Harville and Callanan (1989), a correlation between levels of the grouping factor (e.g., sire) is induced by post-multiplying the incidence matrix of the levels of this random factor by the Cholesky factor of the corresponding (co)variance matrix (e.g., the numerator relationship matrix between sires). Estimation methods available in pedigreemm include approximations to maximum likelihood and REML. This note describes the classes of models that can be fitted using pedigreemm and presents examples that illustrate its use.

Fitting Linear Mixed-Effects Models Using lme4

Abstract: Maximum likelihood or restricted maximum likelihood (REML) estimates of the parameters in linear mixed-effects models can be determined using the lmer function in the lme4 package for R. As for most model-fitting functions in R, the model is described in an lmer call by a formula, in this case including both fixed- and random-effects terms. The formula and data together determine a numerical representation of the model from which the profiled deviance or the profiled REML criterion can be evaluated as a function of some of the model parameters. The appropriate criterion is optimized, using one of the constrained optimization functions in R, to provide the parameter estimates. We describe the structure of the model, the steps in evaluating the profiled deviance or REML criterion, and the structure of classes or types that represents such a model. Sufficient detail is included to allow specialization of these structures by users who wish to write functions to fit specialized linear mixed models, such as models incorporating pedigrees or smoothing splines, that are not easily expressible in the formula language used by lmer.

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Abstract: In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html .

edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.

Abstract: Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org).

limma powers differential expression analyses for RNA-sequencing and microarray studies

Abstract: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Abstract: In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-Seq data, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data. DESeq2 uses shrinkage estimation for dispersions and fold changes to improve stability and interpretability of the estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression and facilitates downstream tasks such as gene ranking and visualization. DESeq2 is available as an R/Bioconductor package.