Expectation Propagation for Approximate Inference: Free Probability Framework

We study asymptotic properties of expectation propagation (EP) -- a method for approximate inference originally developed in the field of machine learning. Applied to generalized linear models, EP iteratively computes a multivariate Gaussian approximation to the exact posterior distribution. The computational complexity of the repeated update of covariance matrices severely limits the application of EP to large problem sizes. In this study, we present a rigorous analysis by means of free probability theory that allows us to overcome this computational bottleneck if specific data matrices in the problem fulfill certain properties of asymptotic freeness. We demonstrate the relevance of our approach on the gene selection problem of a microarray dataset.Comment: Both authors are co-first authors. The main body of this paper is accepted for publication in the proceedings of the 2018 IEEE International Symposium on Information Theory (ISIT

Factored expectation propagation for input-output FHMM models in systems biology

We consider the problem of joint modelling of metabolic signals and gene expression in systems biology applications. We propose an approach based on input-output factorial hidden Markov models and propose a structured variational inference approach to infer the structure and states of the model. We start from the classical free form structured variational mean field approach and use a expectation propagation to approximate the expectations needed in the variational loop. We show that this corresponds to a factored expectation constrained approximate inference. We validate our model through extensive simulations and demonstrate its applicability on a real world bacterial data set

ProbCD: enrichment analysis accounting for categorization uncertainty

As in many other areas of science, systems biology makes extensive use of statistical association and significance estimates in contingency tables, a type of categorical data analysis known in this field as enrichment (also over-representation or enhancement) analysis. In spite of efforts to create probabilistic annotations, especially in the Gene Ontology context, or to deal with uncertainty in high throughput-based datasets, current enrichment methods largely ignore this probabilistic information since they are mainly based on variants of the Fisher Exact Test. We developed an open-source R package to deal with probabilistic categorical data analysis, ProbCD, that does not require a static contingency table. The contingency table for
the enrichment problem is built using the expectation of a Bernoulli Scheme stochastic process given the categorization probabilities. An on-line interface was created to allow usage by non-programmers and is available at: http://xerad.systemsbiology.net/ProbCD/. We present an analysis framework and software tools to address the issue of uncertainty in categorical data analysis. In particular, concerning the enrichment analysis, ProbCD can accommodate: (i) the stochastic nature of the high-throughput experimental techniques and (ii) probabilistic gene annotation

Learning a Hybrid Architecture for Sequence Regression and Annotation

When learning a hidden Markov model (HMM), sequen- tial observations can often be complemented by real-valued summary response variables generated from the path of hid- den states. Such settings arise in numerous domains, includ- ing many applications in biology, like motif discovery and genome annotation. In this paper, we present a flexible frame- work for jointly modeling both latent sequence features and the functional mapping that relates the summary response variables to the hidden state sequence. The algorithm is com- patible with a rich set of mapping functions. Results show that the availability of additional continuous response vari- ables can simultaneously improve the annotation of the se- quential observations and yield good prediction performance in both synthetic data and real-world datasets.Comment: AAAI 201

Large-scale inference and graph theoretical analysis of gene-regulatory networks in B. stubtilis

We present the methods and results of a two-stage modeling process that generates candidate gene-regulatory networks of the bacterium B. subtilis from experimentally obtained, yet mathematically underdetermined microchip array data. By employing a computational, linear correlative procedure to generate these networks, and by analyzing the networks from a graph theoretical perspective, we are able to verify the biological viability of our inferred networks, and we demonstrate that our networks' graph theoretical properties are remarkably similar to those of other biological systems. In addition, by comparing our inferred networks to those of a previous, noisier implementation of the linear inference process [17], we are able to identify trends in graph theoretical behavior that occur both in our networks as well as in their perturbed counterparts. These commonalities in behavior at multiple levels of complexity allow us to ascertain the level of complexity to which our process is robust to noise.Comment: 22 pages, 4 figures, accepted for publication in Physica A (2006

Clustering Algorithms: Their Application to Gene Expression Data

Gene expression data hide vital information required to understand the biological process that takes place in a particular organism in relation to its environment. Deciphering the hidden patterns in gene expression data proffers a prodigious preference to strengthen the understanding of functional genomics. The complexity of biological networks and the volume of genes present increase the challenges of comprehending and interpretation of the resulting mass of data, which consists of millions of measurements; these data also inhibit vagueness, imprecision, and noise. Therefore, the use of clustering techniques is a first step toward addressing these challenges, which is essential in the data mining process to reveal natural structures and iden-tify interesting patterns in the underlying data. The clustering of gene expression data has been proven to be useful in making known the natural structure inherent in gene expression data, understanding gene functions, cellular processes, and subtypes of cells, mining useful information from noisy data, and understanding gene regulation. The other benefit of clustering gene expression data is the identification of homology, which is very important in vaccine design. This review examines the various clustering algorithms applicable to the gene expression data in order to discover and provide useful knowledge of the appropriate clustering technique that will guarantee stability and high degree of accuracy in its analysis procedure

Hierarchic Bayesian models for kernel learning

The integration of diverse forms of informative data by learning an optimal combination of base kernels in classification or regression problems can provide enhanced performance when compared to that obtained from any single data source. We present a Bayesian hierarchical model which enables kernel learning and present effective variational Bayes estimators for regression and classification. Illustrative experiments demonstrate the utility of the proposed method