BioDynaMo is a biological processes simulator developed by an international community of researchers and software engineers working closely with neuroscientists. The authors have taken part in the development of the physical engine, and they are currently working on gene expression, i.e. the process by which the heritable information in a gene - the sequence of DNA base pairs - is made into a functional gene product, such as protein or RNA. Typically, gene regulatory models employ either statistical or analytical approaches, being the former already well understood and broadly used. In this paper, we utilize analytical approaches representing the regulatory networks by means of differential equations, such as Euler and Runge-Kutta methods. The two solutions are implemented in the BioDynaMo project and are compared for accuracy and performance.
The research @cite_25 introduces a new statistical gene network estimation method based on the dynamic Bayesian network and nonparametric regression model with advantages over Bayesian and Boolean networks. For example, it can detect nonlinear dependencies. This article can be taken into consideration in further work if the statistical approach will be implemented in BioDynaMo.
@cite_25
2116290764 2159944419 2148289138 2132663737
We propose a dynamic Bayesian network and nonparametric regression model for constructing a gene network from time series microarray gene expression data. The proposed method can overcome a shortcoming of the Bayesian network model in the sense of the construction of cyclic regulations. The proposed method can analyze the microarray data as a continuous data and can capture even nonlinear relations among genes. It can be expected that this model will give a deeper insight into complicated biological systems. We also derive a new criterion for evaluating an estimated network from Bayes approach. We conduct Monte Carlo experiments to examine the effectiviness of the proposed method. We also demonstrate the proposed method through the analysis of the Saccharomyces cerevisiae gene expression data. Motivation: Inferring networks of proteins from biological data is a central issue of computational biology. Most network inference methods, including Bayesian networks, take unsupervised approaches in which the network is totally unknown in the beginning, and all the edges have to be predicted. A more realistic supervised framework, proposed recently, assumes that a substantial part of the network is known. We propose a new kernel-based method for supervised graph inference based on multiple types of biological datasets such as gene expression, phylogenetic profiles and amino acid sequences. Notably, our method assigns a weight to each type of dataset and thereby selects informative ones. Data selection is useful for reducing data collection costs. For example, when a similar network inference problem must be solved for other organisms, the dataset excluded by our algorithm need not be collected. Results: First, we formulate supervised network inference as a kernel matrix completion problem, where the inference of edges boils down to estimation of missing entries of a kernel matrix. Then, an expectation--maximization algorithm is proposed to simultaneously infer the missing entries of the kernel matrix and the weights of multiple datasets. By introducing the weights, we can integrate multiple datasets selectively and thereby exclude irrelevant and noisy datasets. Our approach is favorably tested in two biological networks: a metabolic network and a protein interaction network. Availability: Software is available on request. Contact: kato-tsuyoshi@aist.go.jp Supplementary information: A supplementary report including mathematical details is available at www.cbrc.jp kato faem faem.html Motivated by analysis of genetical genomics data, we introduce a sparse high-dimensional multivariate regression model for studying conditional independence relationships among a set of genes adjusting for possible genetic effects. The precision matrix in the model specifies a covariate-adjusted Gaussian graph, which presents the conditional dependence structure of gene expression after the confounding genetic effects on gene expression are taken into account. We present a covariate-adjusted precision matrix estimation method using a constrained e 1 minimization, which can be easily implemented by linear programming. Asymptotic convergence rates in various matrix norms and sign consistency are established for the estimators of the regression coefficients and the precision matrix, allowing both the number of genes and the number of the genetic variants to diverge. Simulation shows that the proposed method results in significant improvements in both precision matrix estimation and graphical structure selection when compared to the standard Gaussian graphical model assuming constant means. The proposed method is applied to yeast genetical genomics data for the identification of the gene network among a set of genes in the mitogen-activated protein kinase pathway. Copyright 2013, Oxford University Press. We consider the problem of discovering gene regulatory networks from time-series microarray data. Recently, graphical Granger modeling has gained considerable attention as a promising direction for addressing this problem. These methods apply graphical modeling methods on time-series data and invoke the notion of ‘Granger causality’ to make assertions on causality through inference on time-lagged effects. Existing algorithms, however, have neglected an important aspect of the problem—the group structure among the lagged temporal variables naturally imposed by the time series they belong to. Specifically, existing methods in computational biology share this shortcoming, as well as additional computational limitations, prohibiting their effective applications to the large datasets including a large number of genes and many data points. In the present article, we propose a novel methodology which we term ‘grouped graphical Granger modeling method’, which overcomes the limitations mentioned above by applying a regression method suited for high-dimensional and large data, and by leveraging the group structure among the lagged temporal variables according to the time series they belong to. We demonstrate the effectiveness of the proposed methodology on both simulated and actual gene expression data, specifically the human cancer cell (HeLa S3) cycle data. The simulation results show that the proposed methodology generally exhibits higher accuracy in recovering the underlying causal structure. Those on the gene expression data demonstrate that it leads to improved accuracy with respect to prediction of known links, and also uncovers additional causal relationships uncaptured by earlier works. Contact: aclozano@us.ibm.com