Combining Bayesian Approaches and Evolutionary Techniques for the Inference of Breast Cancer Networks

Gene and protein networks are very important to model complex large-scale systems in molecular biology. Inferring or reverseengineering such networks can be defined as the process of identifying gene/protein interactions from experimental data through computational analysis. However, this task is typically complicated by the enormously large scale of the unknowns in a rather small sample size. Furthermore, when the goal is to study causal relationships within the network, tools capable of overcoming the limitations of correlation networks are required. In this work, we make use of Bayesian Graphical Models to attach this problem and, specifically, we perform a comparative study of different state-of-the-art heuristics, analyzing their performance in inferring the structure of the Bayesian Network from breast cancer data

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

Discovering Graphical Granger Causality Using the Truncating Lasso Penalty

Components of biological systems interact with each other in order to carry out vital cell functions. Such information can be used to improve estimation and inference, and to obtain better insights into the underlying cellular mechanisms. Discovering regulatory interactions among genes is therefore an important problem in systems biology. Whole-genome expression data over time provides an opportunity to determine how the expression levels of genes are affected by changes in transcription levels of other genes, and can therefore be used to discover regulatory interactions among genes. In this paper, we propose a novel penalization method, called truncating lasso, for estimation of causal relationships from time-course gene expression data. The proposed penalty can correctly determine the order of the underlying time series, and improves the performance of the lasso-type estimators. Moreover, the resulting estimate provides information on the time lag between activation of transcription factors and their effects on regulated genes. We provide an efficient algorithm for estimation of model parameters, and show that the proposed method can consistently discover causal relationships in the large $p$, small $n$ setting. The performance of the proposed model is evaluated favorably in simulated, as well as real, data examples. The proposed truncating lasso method is implemented in the R-package grangerTlasso and is available at http://www.stat.lsa.umich.edu/~shojaie.Comment: 12 pages, 4 figures, 1 tabl