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Modern hypothesis testing problems involve a large collection of hypotheses H_1 ..., H_N. The Bayesian local false discovery rate is the posterior probability that a hypothesis is null. The local false discovery rate paradigm is therefore an intuitive and attractive approach for deciding which hypotheses to declare as non-null. Accurate local false discovery rate estimation relies on positing an appropriate null distribution, which should be empirically estimated. It is often reasonable to estimate the null distribution from data that is truncated over a region which can safely deemed to be null. This truncation approach is appealing since it enriches the class of models that can be used as candidate null distributions. We propose the use of a log-concave null distribution as a non-parametric extension of earlier local false discovery rate work. Moreover, the truncation approach has a missing data interpretation. For exponential families, a general but simple EM algorithm can be constructed to obtain the maximum likelihood estimates without having to solve the corresponding score equations, which may be awkward in the case of truncation. We verify the correctness of the algorithm by applying Louis' formula (1982).
Statisticians have met the need to test hundreds or thousands of genomics hypotheses simultaneously with novel empirical Bayes methods that combine advantages of traditional Bayesian and frequentist statistics. Techniques for estimating the local false discovery rate assign probabilities of differential gene expression, genetic association, etc. without requiring subjective prior distributions. This book brings these methods to scientists while keeping the mathematics at an elementary level. Readers will learn the fundamental concepts behind local false discovery rates, preparing them to analyze their own genomics data and to critically evaluate published genomics research. Key Features: * dice games and exercises, including one using interactive software, for teaching the concepts in the classroom * examples focusing on gene expression and on genetic association data and briefly covering metabolomics data and proteomics data * gradual introduction to the mathematical equations needed * how to choose between different methods of multiple hypothesis testing * how to convert the output of genomics hypothesis testing software to estimates of local false discovery rates * guidance through the minefield of current criticisms of p values * material on non-Bayesian prior p values and posterior p values not previously published
We live in a new age for statistical inference, where modern scientific technology such as microarrays and fMRI machines routinely produce thousands and sometimes millions of parallel data sets, each with its own estimation or testing problem. Doing thousands of problems at once is more than repeated application of classical methods. Taking an empirical Bayes approach, Bradley Efron, inventor of the bootstrap, shows how information accrues across problems in a way that combines Bayesian and frequentist ideas. Estimation, testing and prediction blend in this framework, producing opportunities for new methodologies of increased power. New difficulties also arise, easily leading to flawed inferences. This book takes a careful look at both the promise and pitfalls of large-scale statistical inference, with particular attention to false discovery rates, the most successful of the new statistical techniques. Emphasis is on the inferential ideas underlying technical developments, illustrated using a large number of real examples.
Modern scientific technology such as microarrays, imaging devices, genome-wide association studies or social science surveys provide statisticians with hundreds or even thousands of tests to consider simultaneously. Testing many thousands of null hypotheses may increase the number of Type $I$ errors. In large-scale hypothesis testing, researchers can use different statistical techniques such as family-wise error rates, false discovery rates, permutation methods, local false discovery rate, where all available data usually should be analyzed together. In applications, the thousands of tests are related by a scientifically meaningful structure. Ignoring that structure can be misleading as it may increase the number of false positives and false negatives. As an example, in genome-wide association studies each test corresponds to a specific genetic marker. In such a case, the scientific structure for each genetic marker can be its minor allele frequency. In this research, the local false discovery rate as a relevant statistical approach is considered to analyze the thousands of tests together. We present a model for multiple hypothesis testing when the scientific structure of each test is incorporated as a co-variate. The purpose of this model is to incorporate the co-variate to improve the performance of testing procedures. The method we consider has different estimates depending on the tuning parameter. We would like to estimate the optimal value of that parameter by considering observed statistics. Thus, among those estimators, the one which minimizes the estimated errors due to bias and to variance is chosen by applying the bootstrap approach. Such an estimation method is called an adaptive reference class method. Under the combined reference class method, the effect of the co-variates is ignored and all null hypotheses should be analyzed together. In this research, under some assumptions for the co-variates and the prior probabilities, the proposed adaptive reference class method shows smaller error than the combined reference class method in estimating the local false discovery rate, when the number of tests gets large. We describe the adaptive reference class method to the coronary artery disease data, and we use simulation data to evaluate the performance of the estimator associated with the adaptive reference class method.
Data containing large number of variables is becoming increasingly more common and sparsity inducing penalized regression methods, such the lasso, have become a popular analysis tool for these datasets due to their ability to naturally perform variable selection. However, quantifying the importance of the variables selected by these models is a difficult task. These difficulties are compounded by the tendency for the most predictive models, for example those which were chosen using procedures like cross-validation, to include substantial amounts of noise variables with no real relationship with the outcome. To address the task of performing inference on penalized regression models, this thesis proposes false discovery rate approaches for a broad class of penalized regression models. This work includes the development of an upper bound for the number of noise variables in a model, as well as local false discovery rate approaches that quantify the likelihood of each individual selection being a false discovery. These methods are applicable to a wide range of penalties, such as the lasso, elastic net, SCAD, and MCP; a wide range of models, including linear regression, generalized linear models, and Cox proportional hazards models; and are also extended to the group regression setting under the group lasso penalty. In addition to studying these methods using numerous simulation studies, the practical utility of these methods is demonstrated using real data from several high-dimensional genome wide association studies.
Fundamentals of Brain Network Analysis is a comprehensive and accessible introduction to methods for unraveling the extraordinary complexity of neuronal connectivity. From the perspective of graph theory and network science, this book introduces, motivates and explains techniques for modeling brain networks as graphs of nodes connected by edges, and covers a diverse array of measures for quantifying their topological and spatial organization. It builds intuition for key concepts and methods by illustrating how they can be practically applied in diverse areas of neuroscience, ranging from the analysis of synaptic networks in the nematode worm to the characterization of large-scale human brain networks constructed with magnetic resonance imaging. This text is ideally suited to neuroscientists wanting to develop expertise in the rapidly developing field of neural connectomics, and to physical and computational scientists wanting to understand how these quantitative methods can be used to understand brain organization. Winner of the 2017 PROSE Award in Biomedicine & Neuroscience and the 2017 British Medical Association (BMA) Award in Neurology Extensively illustrated throughout by graphical representations of key mathematical concepts and their practical applications to analyses of nervous systems Comprehensively covers graph theoretical analyses of structural and functional brain networks, from microscopic to macroscopic scales, using examples based on a wide variety of experimental methods in neuroscience Designed to inform and empower scientists at all levels of experience, and from any specialist background, wanting to use modern methods of network science to understand the organization of the brain
In an age where the amount of data collected from brain imaging is increasing constantly, it is of critical importance to analyse those data within an accepted framework to ensure proper integration and comparison of the information collected. This book describes the ideas and procedures that underlie the analysis of signals produced by the brain. The aim is to understand how the brain works, in terms of its functional architecture and dynamics. This book provides the background and methodology for the analysis of all types of brain imaging data, from functional magnetic resonance imaging to magnetoencephalography. Critically, Statistical Parametric Mapping provides a widely accepted conceptual framework which allows treatment of all these different modalities. This rests on an understanding of the brain's functional anatomy and the way that measured signals are caused experimentally. The book takes the reader from the basic concepts underlying the analysis of neuroimaging data to cutting edge approaches that would be difficult to find in any other source. Critically, the material is presented in an incremental way so that the reader can understand the precedents for each new development. This book will be particularly useful to neuroscientists engaged in any form of brain mapping; who have to contend with the real-world problems of data analysis and understanding the techniques they are using. It is primarily a scientific treatment and a didactic introduction to the analysis of brain imaging data. It can be used as both a textbook for students and scientists starting to use the techniques, as well as a reference for practicing neuroscientists. The book also serves as a companion to the software packages that have been developed for brain imaging data analysis. An essential reference and companion for users of the SPM software Provides a complete description of the concepts and procedures entailed by the analysis of brain images Offers full didactic treatment of the basic mathematics behind the analysis of brain imaging data Stands as a compendium of all the advances in neuroimaging data analysis over the past decade Adopts an easy to understand and incremental approach that takes the reader from basic statistics to state of the art approaches such as Variational Bayes Structured treatment of data analysis issues that links different modalities and models Includes a series of appendices and tutorial-style chapters that makes even the most sophisticated approaches accessible
Presents a new approach to causal inference and explanation, addressing both the timing and complexity of relationships.
Many modern statistical problems require making similar decisions or estimates for many different entities. For example, we may ask whether each of 10,000 genes is associated with some disease, or try to measure the degree to which each is associated with the disease. As in this example, the entities can often be divided into a vast majority of "null" objects and a small minority of interesting ones. Empirical Bayes is a useful technique for such situations, but finding the right empirical Bayes method for each problem can be difficult. Mixture models, however, provide an easy and effective way to apply empirical Bayes. This thesis motivates mixture models by analyzing a simple high-dimensional problem, and shows their practical use by applying them to detecting single nucleotide polymorphisms.