Bayesian mixture regression analysis for regulation of Pluripotency in ES cells.

BACKGROUND: Observed levels of gene expression strongly depend on both activity of DNA binding transcription factors (TFs) and chromatin state through different histone modifications (HMs). In order to recover the functional relationship between local chromatin state, TF binding and observed levels of gene expression, regression methods have proven to be useful tools. They have been successfully applied to predict mRNA levels from genome-wide experimental data and they provide insight into context-dependent gene regulatory mechanisms. However, heterogeneity arising from gene-set specific regulatory interactions is often overlooked. RESULTS: We show that regression models that predict gene expression by using experimentally derived ChIP-seq profiles of TFs can be significantly improved by mixture modelling. In order to find biologically relevant gene clusters, we employ a Bayesian allocation procedure which allows us to integrate additional biological information such as three-dimensional nuclear organization of chromosomes and gene function. The data integration procedure involves transforming the additional data into gene similarity values. We propose a generic similarity measure that is especially suitable for situations where the additional data are of both continuous and discrete type, and compare its performance with similar measures in the context of mixture modelling. CONCLUSIONS: We applied the proposed method on a data from mouse embryonic stem cells (ESC). We find that including additional data results in mixture components that exhibit biologically meaningful gene clusters, and provides valuable insight into the heterogeneity of the regulatory interactions.

Reconstruction of molecular network evolution from cross-sectional omics data.

Cross-sectional studies may shed light on the evolution of a disease like cancer through the comparison of patient traits among disease stages. This problem is especially challenging when a gene-gene interaction network needs to be reconstructed from omics data, and, in addition, the patients of each stage need not form a homogeneous group. Here, the problem is operationalized as the estimation of stage-wise mixtures of Gaussian graphical models (GGMs) from high-dimensional data. These mixtures are fitted by a (fused) ridge penalized EM algorithm. The fused ridge penalty shrinks GGMs of contiguous stages. The (fused) ridge penalty parameters are chosen through cross-validation. The proposed estimation procedures are shown to be consistent and their performance in other respects is studied in simulation. The down-stream exploitation of the fitted GGMs is outlined. In a data illustration the methodology is employed to identify gene-gene interaction network changes in the transition from normal to cancer prostate tissue.

Analysis of Twitter data with the Bayesian fused graphical lasso.

We propose a method to simplify textual Twitter data into understandable networks of terms that can signify important events and their possible changes over time. The method allows for common characteristics of the networks across time periods and each period can comprise multiple unknown sub-networks. The networks are described by Gaussian graphical models and their parameter values are estimated through a Bayesian approach with a fused lasso-type prior on the precision matrices of the underlying mixtures of the sub-models. A flexible data allocation scheme is at the heart of an MCMC algorithm to recover mean and covariance parameters of the mixture components. Several implementations of the outlined estimation procedure are studied and compared based on simulated data. The procedure with the highest predictive power is used for mining tweets regarding the 2009 Iranian presidential election.

Informative Bayesian Model Selection: a method for identifying interactions in genome-wide data.

In high-dimensional genome-wide (GWA) data, a key challenge is to detect genomic variants that interact in a nonlinear fashion in their association with disease. Identifying such genomic interactions is important for elucidating the inheritance of complex phenotypes and diseases. In this paper, we introduce a new computational method called Informative Bayesian Model Selection (IBMS) that leverages correlation among variants in GWA data due to the linkage disequilibrium to identify interactions accurately in a computationally efficient manner. IBMS combines several statistical methods including canonical correlation analysis, logistic regression analysis, and a Bayesians statistical measure of evaluating interactions. Compared to BOOST and BEAM that are two widely used methods for detecting genomic interactions, IBMS had significantly higher power when evaluated on synthetic data. Furthermore, when applied to Alzheimer's disease GWA data, IBMS identified previously reported interactions. IBMS is a useful method for identifying variants in GWA data, and software that implements IBMS is freely available online from http://lbb.ut.ac.ir/Download/LBBsoft/IBMS.