Network estimation in State Space Model with L1-regularization constraint

Biological networks have arisen as an attractive paradigm of genomic science ever since the introduction of large scale genomic technologies which carried the promise of elucidating the relationship in functional genomics. Microarray technologies coupled with appropriate mathematical or statistical models have made it possible to identify dynamic regulatory networks or to measure time course of the expression level of many genes simultaneously. However one of the few limitations fall on the high-dimensional nature of such data coupled with the fact that these gene expression data are known to include some hidden process. In that regards, we are concerned with deriving a method for inferring a sparse dynamic network in a high dimensional data setting. We assume that the observations are noisy measurements of gene expression in the form of mRNAs, whose dynamics can be described by some unknown or hidden process. We build an input-dependent linear state space model from these hidden states and demonstrate how an incorporated $L_{1}$ regularization constraint in an Expectation-Maximization (EM) algorithm can be used to reverse engineer transcriptional networks from gene expression profiling data. This corresponds to estimating the model interaction parameters. The proposed method is illustrated on time-course microarray data obtained from a well established T-cell data. At the optimum tuning parameters we found genes TRAF5, JUND, CDK4, CASP4, CD69, and C3X1 to have higher number of inwards directed connections and FYB, CCNA2, AKT1 and CASP8 to be genes with higher number of outwards directed connections. We recommend these genes to be object for further investigation. Caspase 4 is also found to activate the expression of JunD which in turn represses the cell cycle regulator CDC2.Comment: arXiv admin note: substantial text overlap with arXiv:1308.359

A Posterior Probability Approach for Gene Regulatory Network Inference in Genetic Perturbation Data

Inferring gene regulatory networks is an important problem in systems biology. However, these networks can be hard to infer from experimental data because of the inherent variability in biological data as well as the large number of genes involved. We propose a fast, simple method for inferring regulatory relationships between genes from knockdown experiments in the NIH LINCS dataset by calculating posterior probabilities, incorporating prior information. We show that the method is able to find previously identified edges from TRANSFAC and JASPAR and discuss the merits and limitations of this approach

Bayesian Regularisation in Structured Additive Regression Models for Survival Data

During recent years, penalized likelihood approaches have attracted a lot of interest both in the area of semiparametric regression and for the regularization of high-dimensional regression models. In this paper, we introduce a Bayesian formulation that allows to combine both aspects into a joint regression model with a focus on hazard regression for survival times. While Bayesian penalized splines form the basis for estimating nonparametric and flexible time-varying effects, regularization of high-dimensional covariate vectors is based on scale mixture of normals priors. This class of priors allows to keep a (conditional) Gaussian prior for regression coefficients on the predictor stage of the model but introduces suitable mixture distributions for the Gaussian variance to achieve regularization. This scale mixture property allows to device general and adaptive Markov chain Monte Carlo simulation algorithms for fitting a variety of hazard regression models. In particular, unifying algorithms based on iteratively weighted least squares proposals can be employed both for regularization and penalized semiparametric function estimation. Since sampling based estimates do no longer have the variable selection property well-known for the Lasso in frequentist analyses, we additionally consider spike and slab priors that introduce a further mixing stage that allows to separate between influential and redundant parameters. We demonstrate the different shrinkage properties with three simulation settings and apply the methods to the PBC Liver dataset