40,125 research outputs found
Exploiting network topology for large-scale inference of nonlinear reaction models
The development of chemical reaction models aids understanding and prediction
in areas ranging from biology to electrochemistry and combustion. A systematic
approach to building reaction network models uses observational data not only
to estimate unknown parameters, but also to learn model structure. Bayesian
inference provides a natural approach to this data-driven construction of
models. Yet traditional Bayesian model inference methodologies that numerically
evaluate the evidence for each model are often infeasible for nonlinear
reaction network inference, as the number of plausible models can be
combinatorially large. Alternative approaches based on model-space sampling can
enable large-scale network inference, but their realization presents many
challenges. In this paper, we present new computational methods that make
large-scale nonlinear network inference tractable. First, we exploit the
topology of networks describing potential interactions among chemical species
to design improved "between-model" proposals for reversible-jump Markov chain
Monte Carlo. Second, we introduce a sensitivity-based determination of move
types which, when combined with network-aware proposals, yields significant
additional gains in sampling performance. These algorithms are demonstrated on
inference problems drawn from systems biology, with nonlinear differential
equation models of species interactions
NetDiff – Bayesian model selection for differential gene regulatory network inference
Differential networks allow us to better understand the changes in cellular processes that are exhibited in conditions of interest, identifying variations in gene regulation or protein interaction between, for example, cases and controls, or in response to external stimuli. Here we present a novel methodology for the inference of differential gene regulatory networks from gene expression microarray data. Specifically we apply a Bayesian model selection approach to compare models of conserved and varying network structure, and use Gaussian graphical models to represent the network structures. We apply a variational inference approach to the learning of Gaussian graphical models of gene regulatory networks, that enables us to perform Bayesian model selection that is significantly more computationally efficient than Markov Chain Monte Carlo approaches. Our method is demonstrated to be more robust than independent analysis of data from multiple conditions when applied to synthetic network data, generating fewer false positive predictions of differential edges. We demonstrate the utility of our approach on real world gene expression microarray data by applying it to existing data from amyotrophic lateral sclerosis cases with and without mutations in C9orf72, and controls, where we are able to identify differential network interactions for further investigation
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
Parametric and non-parametric gradient matching for network inference:a comparison
Abstract Background Reverse engineering of gene regulatory networks from time series gene-expression data is a challenging problem, not only because of the vast sets of candidate interactions but also due to the stochastic nature of gene expression. We limit our analysis to nonlinear differential equation based inference methods. In order to avoid the computational cost of large-scale simulations, a two-step Gaussian process interpolation based gradient matching approach has been proposed to solve differential equations approximately. Results We apply a gradient matching inference approach to a large number of candidate models, including parametric differential equations or their corresponding non-parametric representations, we evaluate the network inference performance under various settings for different inference objectives. We use model averaging, based on the Bayesian Information Criterion (BIC), to combine the different inferences. The performance of different inference approaches is evaluated using area under the precision-recall curves. Conclusions We found that parametric methods can provide comparable, and often improved inference compared to non-parametric methods; the latter, however, require no kinetic information and are computationally more efficient
Joint estimation of multiple related biological networks
Graphical models are widely used to make inferences concerning interplay in
multivariate systems. In many applications, data are collected from multiple
related but nonidentical units whose underlying networks may differ but are
likely to share features. Here we present a hierarchical Bayesian formulation
for joint estimation of multiple networks in this nonidentically distributed
setting. The approach is general: given a suitable class of graphical models,
it uses an exchangeability assumption on networks to provide a corresponding
joint formulation. Motivated by emerging experimental designs in molecular
biology, we focus on time-course data with interventions, using dynamic
Bayesian networks as the graphical models. We introduce a computationally
efficient, deterministic algorithm for exact joint inference in this setting.
We provide an upper bound on the gains that joint estimation offers relative to
separate estimation for each network and empirical results that support and
extend the theory, including an extensive simulation study and an application
to proteomic data from human cancer cell lines. Finally, we describe
approximations that are still more computationally efficient than the exact
algorithm and that also demonstrate good empirical performance.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS761 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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