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
 .

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

The second edition of this acclaimed graduate text provides a unified treatment of two methods used in contemporary econometric research, cross section and data panel methods. By focusing on assumptions that can be given behavioral content, the book maintains an appropriate level of rigor while emphasizing intuitive thinking. The analysis covers both linear and nonlinear models, including models with dynamics and/or individual heterogeneity. In addition to general estimation frameworks (particular methods of moments and maximum likelihood), specific linear and nonlinear methods are covered in detail, including probit and logit models and their multivariate, Tobit models, models for count data, censored and missing data schemes, causal (or treatment) effects, and duration analysis. Econometric Analysis of Cross Section and Panel Data was the first graduate econometrics text to focus on microeconomic data structures, allowing assumptions to be separated into population and sampling assumptions. This second edition has been substantially updated and revised. Improvements include a broader class of models for missing data problems; more detailed treatment of cluster problems, an important topic for empirical researchers; expanded discussion of "generalized instrumental variables" (GIV) estimation; new coverage (based on the author's own recent research) of inverse probability weighting; a more complete framework for estimating treatment effects with panel data, and a firmly established link between econometric approaches to nonlinear panel data and the "generalized estimating equation" literature popular in statistics and other fields. New attention is given to explaining when particular econometric methods can be applied; the goal is not only to tell readers what does work, but why certain "obvious" procedures do not. The numerous included exercises, both theoretical and computer-based, allow the reader to extend methods covered in the text and discover new insights.

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Econometric Analysis of Cross Section and Panel Data

The technique of iterative weighted linear regression can be used to obtain maximum likelihood estimates of the parameters with observations distributed according to some exponential family and systematic effects that can be made linear by a suitable transformation. A generalization of the analysis of variance is given for these models using log- likelihoods. These generalized linear models are illustrated by examples relating to four distributions; the Normal, Binomial (probit analysis, etc.), Poisson (contingency tables) and gamma (variance components).

Generalized Linear Models

Many problems of recent interest in statistics and machine learning can be posed in the framework of convex optimization. Due to the explosion in size and complexity of modern datasets, it is increasingly important to be able to solve problems with a very large number of features or training examples. As a result, both the decentralized collection or storage of these datasets as well as accompanying distributed solution methods are either necessary or at least highly desirable. In this review, we argue that the alternating direction method of multipliers is well suited to distributed convex optimization, and in particular to large-scale problems arising in statistics, machine learning, and related areas. The method was developed in the 1970s, with roots in the 1950s, and is equivalent or closely related to many other algorithms, such as dual decomposition, the method of multipliers, Douglas–Rachford splitting, Spingarn's method of partial inverses, Dykstra's alternating projections, Bregman iterative algorithms for l1 problems, proximal methods, and others. After briefly surveying the theory and history of the algorithm, we discuss applications to a wide variety of statistical and machine learning problems of recent interest, including the lasso, sparse logistic regression, basis pursuit, covariance selection, support vector machines, and many others. We also discuss general distributed optimization, extensions to the nonconvex setting, and efficient implementation, including some details on distributed MPI and Hadoop MapReduce implementations.

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Distributed Optimization and Statistical Learning Via the Alternating Direction Method of Multipliers

SUMMARY This paper proposes an extension of generalized linear models to the analysis of longitudinal data. We introduce a class of estimating equations that give consistent estimates of the regression parameters and of their variance under mild assumptions about the time dependence. The estimating equations are derived without specifying the joint distribution of a subject's observations yet they reduce to the score equations for multivariate Gaussian outcomes. Asymptotic theory is presented for the general class of estimators. Specific cases in which we assume independence, m-dependence and exchangeable correlation structures from each subject are discussed. Efficiency of the proposed estimators in two simple situations is considered. The approach is closely related to quasi-likelih ood. Some key ironh: Estimating equation; Generalized linear model; Longitudinal data; Quasi-likelihood; Repeated measures.

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Longitudinal data analysis using generalized linear models

Addresses a class of statistical models that generalizes classical linear models-extending them to include many other models useful in statistical analysis. Incorporates numerous exercises, both theoretical and data-analytic Discusses quasi-likelihood functions and estimating equations, models for dispersion effect, components of dispersion, and conditional likelihoods Holds particular interest for statisticians in medicine, biology, agriculture, social science, and engineering

Generalized linear models. 2nd ed.

SUMMARY A general class of regression models for ordinal data is developed and discussed. These models utilize the ordinal nature of the data by describing various modes of stochastic ordering and this eliminates the need for assigning scores or otherwise assuming cardinality instead of ordinality. Two models in particular, the proportional odds and the proportional hazards models are likely to be most useful in practice because of the simplicity of their interpretation. These linear models are shown to be multivariate extensions of generalized linear models. Extensions to non-linear models are discussed and it is shown that even here the method of iteratively reweighted least squares converges to the maximum likelihood estimate, a property which greatly simplifies the necessary computation. Applications are discussed with the aid of examples.

https://rss.onlinelibrary.wiley.com/doi/pdf/10.1111/j.2517-6161.1980.tb01109.x

Regression Models for Ordinal Data

This book provides a systematic development of tensor methods in statistics, beginning with the study of multivariate moments and cumulants. The effect on moment arrays and on cumulant arrays of making linear or affine transformations of the variables is studied. Because of their importance in statistical theory, invariant functions of the cumulants are studied in some detail. This is followed by an examination of the effect of making a polynomial transformation of the original variables. The fundamental operation of summing over complementary set partitions is introduced at this stage. This operation shapes the notation and pervades much of the remainder of the book. The necessary lattice-theory is discussed and suitable tables of complementary set partitions are provided. Subsequent chapters deal with asymptotic approximations based on Edgeworth expansion and saddlepoint expansion. The saddlepoint expansion is introduced via the Legendre transformation of the cumulant generating function, also known as the conjugate function of the cumulant generating function. A recurring them is that, with suitably chosen notation, multivariate calculations are often simpler and more transparent than the corresponding univariate calculations. The final two chapters deal with likelihood ratio statistics, maximum likelihood estimation and the effect on inferences of conditioning on ancillary or approximately ancillary statistics. The Bartlett adjustment factor is derived in the general case and simplified for certain types of generalized linear models. Finally, Barndorff-Nielsen's formula for the conditional distribution of the maximum liklelihood estimator is derived and discussed. More than 200 Exercises are provided to illustrate the uses of tensor methodology.

Peter McCullagh

Papers

Generalized Linear Models

Generalized Linear Models

Generalized linear models. 2nd ed.

Regression Models for Ordinal Data

Tensor Methods in Statistics