This dissertation presents a novel contribution to scientific knowledge in the form of the development of statistical methodology for integrating diverse, genomic data sets, and by contributing to the understanding of the conservation of post- reproductive brain aging in mammals. Broadly speaking, this work is divided into two complimentary sections. The first section describes the development of a mixed effects modeling approach for integrating high-dimensional, genomic data sets. Microarray-based technologies allow researchers to monitor gene expression, transcription factor binding and alternative splicing on a genome-wide scale. The current challenge is to develop methods that analyze and integrate these vast data sets in a manner that produces biologically meaningful results, which can then be experimentally followed-up in the lab. The approach is described in terms of analyzing array data in the context of biologically-related groups of genes. A key component to this approach is the development of a novel model selection strategy that utilizes the biological information contained in the Gene Ontology graph in order to balance between biological specificity and model parsimony.

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

Machine Learning and Medical Imaging presents state-of- the-art machine learning methods in medical image analysis. It first summarizes cutting-edge machine learning algorithms in medical imaging, including not only classical probabilistic modeling and learning methods, but also recent breakthroughs in deep learning, sparse representation/coding, and big data hashing. In the second part leading research groups around the world present a wide spectrum of machine learning methods with application to different medical imaging modalities, clinical domains, and organs. The biomedical imaging modalities include ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), histology, and microscopy images. The targeted organs span the lung, liver, brain, and prostate, while there is also a treatment of examining genetic associations. Machine Learning and Medical Imaging is an ideal reference for medical imaging researchers, industry scientists and engineers, advanced undergraduate and graduate students, and clinicians. - Demonstrates the application of cutting-edge machine learning techniques to medical imaging problems - Covers an array of medical imaging applications including computer assisted diagnosis, image guided radiation therapy, landmark detection, imaging genomics, and brain connectomics - Features self-contained chapters with a thorough literature review - Assesses the development of future machine learning techniques and the further application of existing techniques

Providing a broad but in-depth introduction to neural network and machine learning in a statistical framework, this book provides a single, comprehensive resource for study and further research. All the major popular neural network models and statistical learning approaches are covered with examples and exercises in every chapter to develop a practical working understanding of the content. Each of the twenty-five chapters includes state-of-the-art descriptions and important research results on the respective topics. The broad coverage includes the multilayer perceptron, the Hopfield network, associative memory models, clustering models and algorithms, the radial basis function network, recurrent neural networks, principal component analysis, nonnegative matrix factorization, independent component analysis, discriminant analysis, support vector machines, kernel methods, reinforcement learning, probabilistic and Bayesian networks, data fusion and ensemble learning, fuzzy sets and logic, neurofuzzy models, hardware implementations, and some machine learning topics. Applications to biometric/bioinformatics and data mining are also included. Focusing on the prominent accomplishments and their practical aspects, academic and technical staff, graduate students and researchers will find that this provides a solid foundation and encompassing reference for the fields of neural networks, pattern recognition, signal processing, machine learning, computational intelligence, and data mining.

Praise for the First Edition “This book will serve to greatly complement the growing number of texts dealing with mixed models, and I highly recommend including it in one’s personal library.” —Journal of the American Statistical Association Mixed modeling is a crucial area of statistics, enabling the analysis of clustered and longitudinal data. Mixed Models: Theory and Applications with R, Second Edition fills a gap in existing literature between mathematical and applied statistical books by presenting a powerful examination of mixed model theory and application with special attention given to the implementation in R. The new edition provides in-depth mathematical coverage of mixed models’ statistical properties and numerical algorithms, as well as nontraditional applications, such as regrowth curves, shapes, and images. The book features the latest topics in statistics including modeling of complex clustered or longitudinal data, modeling data with multiple sources of variation, modeling biological variety and heterogeneity, Healthy Akaike Information Criterion (HAIC), parameter multidimensionality, and statistics of image processing. Mixed Models: Theory and Applications with R, Second Edition features unique applications of mixed model methodology, as well as: Comprehensive theoretical discussions illustrated by examples and figures Over 300 exercises, end-of-section problems, updated data sets, and R subroutines Problems and extended projects requiring simulations in R intended to reinforce material Summaries of major results and general points of discussion at the end of each chapter Open problems in mixed modeling methodology, which can be used as the basis for research or PhD dissertations Ideal for graduate-level courses in mixed statistical modeling, the book is also an excellent reference for professionals in a range of fields, including cancer research, computer science, and engineering.