Integrative Model-based clustering of microarray methylation and expression data

In many fields, researchers are interested in large and complex biological processes. Two important examples are gene expression and DNA methylation in genetics. One key problem is to identify aberrant patterns of these processes and discover biologically distinct groups. In this article we develop a model-based method for clustering such data. The basis of our method involves the construction of a likelihood for any given partition of the subjects. We introduce cluster specific latent indicators that, along with some standard assumptions, impose a specific mixture distribution on each cluster. Estimation is carried out using the EM algorithm. The methods extend naturally to multiple data types of a similar nature, which leads to an integrated analysis over multiple data platforms, resulting in higher discriminating power.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS533 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Clustering student skill set profiles in a unit hypercube using mixtures of multivariate betas

<br>This paper presents a finite mixture of multivariate betas as a new model-based clustering method tailored to applications where the feature space is constrained to the unit hypercube. The mixture component densities are taken to be conditionally independent, univariate unimodal beta densities (from the subclass of reparameterized beta densities given by Bagnato and Punzo 2013). The EM algorithm used to fit this mixture is discussed in detail, and results from both this beta mixture model and the more standard Gaussian model-based clustering are presented for simulated skill mastery data from a common cognitive diagnosis model and for real data from the Assistment System online mathematics tutor (Feng et al 2009). The multivariate beta mixture appears to outperform the standard Gaussian model-based clustering approach, as would be expected on the constrained space. Fewer components are selected (by BIC-ICL) in the beta mixture than in the Gaussian mixture, and the resulting clusters seem more reasonable and interpretable.</br> <br>This article is in technical report form, the final publication is available at http://www.springerlink.com/openurl.asp?genre=article &id=doi:10.1007/s11634-013-0149-z</br&gt

Modeling and visualizing uncertainty in gene expression clusters using Dirichlet process mixtures

Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data, little attention has been paid to uncertainty in the results obtained. Dirichlet process mixture (DPM) models provide a nonparametric Bayesian alternative to the bootstrap approach to modeling uncertainty in gene expression clustering. Most previously published applications of Bayesian model-based clustering methods have been to short time series data. In this paper, we present a case study of the application of nonparametric Bayesian clustering methods to the clustering of high-dimensional nontime series gene expression data using full Gaussian covariances. We use the probability that two genes belong to the same cluster in a DPM model as a measure of the similarity of these gene expression profiles. Conversely, this probability can be used to define a dissimilarity measure, which, for the purposes of visualization, can be input to one of the standard linkage algorithms used for hierarchical clustering. Biologically plausible results are obtained from the Rosetta compendium of expression profiles which extend previously published cluster analyses of this data

Decorrelation of Neutral Vector Variables: Theory and Applications

In this paper, we propose novel strategies for neutral vector variable decorrelation. Two fundamental invertible transformations, namely serial nonlinear transformation and parallel nonlinear transformation, are proposed to carry out the decorrelation. For a neutral vector variable, which is not multivariate Gaussian distributed, the conventional principal component analysis (PCA) cannot yield mutually independent scalar variables. With the two proposed transformations, a highly negatively correlated neutral vector can be transformed to a set of mutually independent scalar variables with the same degrees of freedom. We also evaluate the decorrelation performances for the vectors generated from a single Dirichlet distribution and a mixture of Dirichlet distributions. The mutual independence is verified with the distance correlation measurement. The advantages of the proposed decorrelation strategies are intensively studied and demonstrated with synthesized data and practical application evaluations

Probabilistic Graphical Model Representation in Phylogenetics

Recent years have seen a rapid expansion of the model space explored in statistical phylogenetics, emphasizing the need for new approaches to statistical model representation and software development. Clear communication and representation of the chosen model is crucial for: (1) reproducibility of an analysis, (2) model development and (3) software design. Moreover, a unified, clear and understandable framework for model representation lowers the barrier for beginners and non-specialists to grasp complex phylogenetic models, including their assumptions and parameter/variable dependencies. Graphical modeling is a unifying framework that has gained in popularity in the statistical literature in recent years. The core idea is to break complex models into conditionally independent distributions. The strength lies in the comprehensibility, flexibility, and adaptability of this formalism, and the large body of computational work based on it. Graphical models are well-suited to teach statistical models, to facilitate communication among phylogeneticists and in the development of generic software for simulation and statistical inference. Here, we provide an introduction to graphical models for phylogeneticists and extend the standard graphical model representation to the realm of phylogenetics. We introduce a new graphical model component, tree plates, to capture the changing structure of the subgraph corresponding to a phylogenetic tree. We describe a range of phylogenetic models using the graphical model framework and introduce modules to simplify the representation of standard components in large and complex models. Phylogenetic model graphs can be readily used in simulation, maximum likelihood inference, and Bayesian inference using, for example, Metropolis-Hastings or Gibbs sampling of the posterior distribution