Discovering transcriptional modules by Bayesian data integration

Motivation: We present a method for directly inferring transcriptional modules (TMs) by integrating gene expression and transcription factor binding (ChIP-chip) data. Our model extends a hierarchical Dirichlet process mixture model to allow data fusion on a gene-by-gene basis. This encodes the intuition that co-expression and co-regulation are not necessarily equivalent and hence we do not expect all genes to group similarly in both datasets. In particular, it allows us to identify the subset of genes that share the same structure of transcriptional modules in both datasets. Results: We find that by working on a gene-by-gene basis, our model is able to extract clusters with greater functional coherence than existing methods. By combining gene expression and transcription factor binding (ChIP-chip) data in this way, we are better able to determine the groups of genes that are most likely to represent underlying TMs

Mixed membership stochastic blockmodels

Observations consisting of measurements on relationships for pairs of objects arise in many settings, such as protein interaction and gene regulatory networks, collections of author-recipient email, and social networks. Analyzing such data with probabilisic models can be delicate because the simple exchangeability assumptions underlying many boilerplate models no longer hold. In this paper, we describe a latent variable model of such data called the mixed membership stochastic blockmodel. This model extends blockmodels for relational data to ones which capture mixed membership latent relational structure, thus providing an object-specific low-dimensional representation. We develop a general variational inference algorithm for fast approximate posterior inference. We explore applications to social and protein interaction networks.Comment: 46 pages, 14 figures, 3 table

The EM Algorithm and the Rise of Computational Biology

In the past decade computational biology has grown from a cottage industry with a handful of researchers to an attractive interdisciplinary field, catching the attention and imagination of many quantitatively-minded scientists. Of interest to us is the key role played by the EM algorithm during this transformation. We survey the use of the EM algorithm in a few important computational biology problems surrounding the "central dogma"; of molecular biology: from DNA to RNA and then to proteins. Topics of this article include sequence motif discovery, protein sequence alignment, population genetics, evolutionary models and mRNA expression microarray data analysis.Comment: Published in at http://dx.doi.org/10.1214/09-STS312 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Computing the likelihood of sequence segmentation under Markov modelling

I tackle the problem of partitioning a sequence into homogeneous segments, where homogeneity is defined by a set of Markov models. The problem is to study the likelihood that a sequence is divided into a given number of segments. Here, the moments of this likelihood are computed through an efficient algorithm. Unlike methods involving Hidden Markov Models, this algorithm does not require probability transitions between the models. Among many possible usages of the likelihood, I present a maximum \textit{a posteriori} probability criterion to predict the number of homogeneous segments into which a sequence can be divided, and an application of this method to find CpG islands

Model selection and sensitivity analysis for sequence pattern models

In this article we propose a maximal a posteriori (MAP) criterion for model selection in the motif discovery problem and investigate conditions under which the MAP asymptotically gives a correct prediction of model size. We also investigate robustness of the MAP to prior specification and provide guidelines for choosing prior hyper-parameters for motif models based on sensitivity considerations.Comment: Published in at http://dx.doi.org/10.1214/193940307000000301 the IMS Collections (http://www.imstat.org/publications/imscollections.htm) by the Institute of Mathematical Statistics (http://www.imstat.org