Inferring gene regulatory networks from gene expression data by a dynamic Bayesian network-based model

Enabled by recent advances in bioinformatics, the inference of gene regulatory networks (GRNs) from gene expression data has garnered much interest from researchers. This is due to the need of researchers to understand the dynamic behavior and uncover the vast information lay hidden within the networks. In this regard, dynamic Bayesian network (DBN) is extensively used to infer GRNs due to its ability to handle time-series microarray data and modeling feedback loops. However, the efficiency of DBN in inferring GRNs is often hampered by missing values in expression data, and excessive computation time due to the large search space whereby DBN treats all genes as potential regulators for a target gene. In this paper, we proposed a DBN-based model with missing values imputation to improve inference efficiency, and potential regulators detection which aims to lessen computation time by limiting potential regulators based on expression changes. The performance of the proposed model is assessed by using time-series expression data of yeast cell cycle. The experimental results showed reduced computation time and improved efficiency in detecting gene-gene relationships

Inferring gene regulatory networks from gene expression data by a dynamic Bayesian network-based model

Enabled by recent advances in bioinformatics, the inference of gene regulatory networks (GRNs) from gene expression data has garnered much interest from researchers. This is due to the need of researchers to understand the dynamic behavior and uncover the vast information lay hidden within the networks. In this regard, dynamic Bayesian network (DBN) is extensively used to infer GRNs due to its ability to handle time-series microarray data and modeling feedback loops. However, the efficiency of DBN in inferring GRNs is often hampered by missing values in expression data, and excessive computation time due to the large search space whereby DBN treats all genes as potential regulators for a target gene. In this paper, we proposed a DBN-based model with missing values imputation to improve inference efficiency, and potential regulators detection which aims to lessen computation time by limiting potential regulators based on expression changes. The performance of the proposed model is assessed by using time-series expression data of yeast cell cycle. The experimental results showed reduced computation time and improved efficiency in detecting gene-gene relationships

State Space Model with hidden variables for reconstruction of gene regulatory networks

<p>Abstract</p> <p>Background</p> <p>State Space Model (SSM) is a relatively new approach to inferring gene regulatory networks. It requires less computational time than Dynamic Bayesian Networks (DBN). There are two types of variables in the linear SSM, observed variables and hidden variables. SSM uses an iterative method, namely Expectation-Maximization, to infer regulatory relationships from microarray datasets. The hidden variables cannot be directly observed from experiments. How to determine the number of hidden variables has a significant impact on the accuracy of network inference. In this study, we used SSM to infer Gene regulatory networks (GRNs) from synthetic time series datasets, investigated Bayesian Information Criterion (BIC) and Principle Component Analysis (PCA) approaches to determining the number of hidden variables in SSM, and evaluated the performance of SSM in comparison with DBN.</p> <p>Method</p> <p>True GRNs and synthetic gene expression datasets were generated by using GeneNetWeaver. Both DBN and linear SSM were used to infer GRNs from the synthetic datasets. The inferred networks were compared with the true networks.</p> <p>Results</p> <p>Our results show that inference precision varied with the number of hidden variables. For some regulatory networks, the inference precision of DBN was higher but SSM performed better in other cases. Although the overall performance of the two approaches is compatible, SSM is much faster and capable of inferring much larger networks than DBN.</p> <p>Conclusion</p> <p>This study provides useful information in handling the hidden variables and improving the inference precision.</p

Inferring Gene Regulatory Networks from Time Series Microarray Data

The innovations and improvements in high-throughput genomic technologies, such as DNA microarray, make it possible for biologists to simultaneously measure dependencies and regulations among genes on a genome-wide scale and provide us genetic information. An important objective of the functional genomics is to understand the controlling mechanism of the expression of these genes and encode the knowledge into gene regulatory network (GRN). To achieve this, computational and statistical algorithms are especially needed. Inference of GRN is a very challenging task for computational biologists because the degree of freedom of the parameters is redundant. Various computational approaches have been proposed for modeling gene regulatory networks, such as Boolean network, differential equations and Bayesian network. There is no so called golden method which can generally give us the best performance for any data set. The research goal is to improve inference accuracy and reduce computational complexity. One of the problems in reconstructing GRN is how to deal with the high dimensionality and short time course gene expression data. In this work, some existing inference algorithms are compared and the limitations lie in that they either suffer from low inference accuracy or computational complexity. To overcome such difficulties, a new approach based on state space model and Expectation-Maximization (EM) algorithms is proposed to model the dynamic system of gene regulation and infer gene regulatory networks. In our model, GRN is represented by a state space model that incorporates noises and has the ability to capture more various biological aspects, such as hidden or missing variables. An EM algorithm is used to estimate the parameters based on the given state space functions and the gene interaction matrix is derived by decomposing the observation matrix using singular value decomposition, and then it is used to infer GRN. The new model is validated using synthetic data sets before applying it to real biological data sets. The results reveal that the developed model can infer the gene regulatory networks from large scale gene expression data and significantly reduce the computational time complexity without losing much inference accuracy compared to dynamic Bayesian network

Identifying interactions in the time and frequency domains in local and global networks : a Granger causality approach

Background Reverse-engineering approaches such as Bayesian network inference, ordinary differential equations (ODEs) and information theory are widely applied to deriving causal relationships among different elements such as genes, proteins, metabolites, neurons, brain areas and so on, based upon multi-dimensional spatial and temporal data. There are several well-established reverse-engineering approaches to explore causal relationships in a dynamic network, such as ordinary differential equations (ODE), Bayesian networks, information theory and Granger Causality. Results Here we focused on Granger causality both in the time and frequency domain and in local and global networks, and applied our approach to experimental data (genes and proteins). For a small gene network, Granger causality outperformed all the other three approaches mentioned above. A global protein network of 812 proteins was reconstructed, using a novel approach. The obtained results fitted well with known experimental findings and predicted many experimentally testable results. In addition to interactions in the time domain, interactions in the frequency domain were also recovered. Conclusions The results on the proteomic data and gene data confirm that Granger causality is a simple and accurate approach to recover the network structure. Our approach is general and can be easily applied to other types of temporal data

Inferring dynamic genetic networks with low order independencies

In this paper, we propose a novel inference method for dynamic genetic networks which makes it possible to face with a number of time measurements n much smaller than the number of genes p. The approach is based on the concept of low order conditional dependence graph that we extend here in the case of Dynamic Bayesian Networks. Most of our results are based on the theory of graphical models associated with the Directed Acyclic Graphs (DAGs). In this way, we define a minimal DAG G which describes exactly the full order conditional dependencies given the past of the process. Then, to face with the large p and small n estimation case, we propose to approximate DAG G by considering low order conditional independencies. We introduce partial qth order conditional dependence DAGs G(q) and analyze their probabilistic properties. In general, DAGs G(q) differ from DAG G but still reflect relevant dependence facts for sparse networks such as genetic networks. By using this approximation, we set out a non-bayesian inference method and demonstrate the effectiveness of this approach on both simulated and real data analysis. The inference procedure is implemented in the R package 'G1DBN' freely available from the CRAN archive

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