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

Bayesian Structure Learning for Markov Random Fields with a Spike and Slab Prior

In recent years a number of methods have been developed for automatically learning the (sparse) connectivity structure of Markov Random Fields. These methods are mostly based on L1-regularized optimization which has a number of disadvantages such as the inability to assess model uncertainty and expensive cross-validation to find the optimal regularization parameter. Moreover, the model's predictive performance may degrade dramatically with a suboptimal value of the regularization parameter (which is sometimes desirable to induce sparseness). We propose a fully Bayesian approach based on a "spike and slab" prior (similar to L0 regularization) that does not suffer from these shortcomings. We develop an approximate MCMC method combining Langevin dynamics and reversible jump MCMC to conduct inference in this model. Experiments show that the proposed model learns a good combination of the structure and parameter values without the need for separate hyper-parameter tuning. Moreover, the model's predictive performance is much more robust than L1-based methods with hyper-parameter settings that induce highly sparse model structures.Comment: Accepted in the Conference on Uncertainty in Artificial Intelligence (UAI), 201