Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling

<p>Abstract</p> <p>Background</p> <p>The reconstruction of gene regulatory networks from time series gene expression data is one of the most difficult problems in systems biology. This is due to several reasons, among them the combinatorial explosion of possible network topologies, limited information content of the experimental data with high levels of noise, and the complexity of gene regulation at the transcriptional, translational and post-translational levels. At the same time, quantitative, dynamic models, ideally with probability distributions over model topologies and parameters, are highly desirable.</p> <p>Results</p> <p>We present a novel approach to infer such models from data, based on nonlinear differential equations, which we embed into a stochastic Bayesian framework. We thus address both the stochasticity of experimental data and the need for quantitative dynamic models. Furthermore, the Bayesian framework allows it to easily integrate prior knowledge into the inference process. Using stochastic sampling from the Bayes' posterior distribution, our approach can infer different likely network topologies and model parameters along with their respective probabilities from given data. We evaluate our approach on simulated data and the challenge #3 data from the DREAM 2 initiative. On the simulated data, we study effects of different levels of noise and dataset sizes. Results on real data show that the dynamics and main regulatory interactions are correctly reconstructed.</p> <p>Conclusions</p> <p>Our approach combines dynamic modeling using differential equations with a stochastic learning framework, thus bridging the gap between biophysical modeling and stochastic inference approaches. Results show that the method can reap the advantages of both worlds, and allows the reconstruction of biophysically accurate dynamic models from noisy data. In addition, the stochastic learning framework used permits the computation of probability distributions over models and model parameters, which holds interesting prospects for experimental design purposes.</p

A cognitive hierarchy model of learning in networks

This paper proposes a method for estimating a hierarchical model of bounded rationality in games of learning in networks. A cognitive hierarchy comprises a set of cognitive types whose behavior ranges from random to substantively rational. SpeciÖcally, each cognitive type in the model corresponds to the number of periods in which economic agents process new information. Using experimental data, we estimate type distributions in a variety of task environments and show how estimated distributions depend on the structural properties of the environments. The estimation results identify signiÖcant levels of behavioral hetero-geneity in the experimental data and overall conÖrm comparative static conjectures on type distributions across task environments. Surprisingly, the model replicates the aggregate pat-terns of the behavior in the data quite well. Finally, we found that the dominant type in the data is closely related to Bayes-rational behavior

A non-homogeneous dynamic Bayesian network with sequentially coupled interaction parameters for applications in systems and synthetic biology

An important and challenging problem in systems biology is the inference of gene regulatory networks from short non-stationary time series of transcriptional profiles. A popular approach that has been widely applied to this end is based on dynamic Bayesian networks (DBNs), although traditional homogeneous DBNs fail to model the non-stationarity and time-varying nature of the gene regulatory processes. Various authors have therefore recently proposed combining DBNs with multiple changepoint processes to obtain time varying dynamic Bayesian networks (TV-DBNs). However, TV-DBNs are not without problems. Gene expression time series are typically short, which leaves the model over-flexible, leading to over-fitting or inflated inference uncertainty. In the present paper, we introduce a Bayesian regularization scheme that addresses this difficulty. Our approach is based on the rationale that changes in gene regulatory processes appear gradually during an organism's life cycle or in response to a changing environment, and we have integrated this notion in the prior distribution of the TV-DBN parameters. We have extensively tested our regularized TV-DBN model on synthetic data, in which we have simulated short non-homogeneous time series produced from a system subject to gradual change. We have then applied our method to real-world gene expression time series, measured during the life cycle of Drosophila melanogaster, under artificially generated constant light condition in Arabidopsis thaliana, and from a synthetically designed strain of Saccharomyces cerevisiae exposed to a changing environment

Joint Structure Learning of Multiple Non-Exchangeable Networks

Several methods have recently been developed for joint structure learning of multiple (related) graphical models or networks. These methods treat individual networks as exchangeable, such that each pair of networks are equally encouraged to have similar structures. However, in many practical applications, exchangeability in this sense may not hold, as some pairs of networks may be more closely related than others, for example due to group and sub-group structure in the data. Here we present a novel Bayesian formulation that generalises joint structure learning beyond the exchangeable case. In addition to a general framework for joint learning, we (i) provide a novel default prior over the joint structure space that requires no user input; (ii) allow for latent networks; (iii) give an efficient, exact algorithm for the case of time series data and dynamic Bayesian networks. We present empirical results on non-exchangeable populations, including a real data example from biology, where cell-line-specific networks are related according to genomic features.Comment: To appear in Proceedings of the Seventeenth International Conference on Artificial Intelligence and Statistics (AISTATS

An Overview on Application of Machine Learning Techniques in Optical Networks

Today's telecommunication networks have become sources of enormous amounts of widely heterogeneous data. This information can be retrieved from network traffic traces, network alarms, signal quality indicators, users' behavioral data, etc. Advanced mathematical tools are required to extract meaningful information from these data and take decisions pertaining to the proper functioning of the networks from the network-generated data. Among these mathematical tools, Machine Learning (ML) is regarded as one of the most promising methodological approaches to perform network-data analysis and enable automated network self-configuration and fault management. The adoption of ML techniques in the field of optical communication networks is motivated by the unprecedented growth of network complexity faced by optical networks in the last few years. Such complexity increase is due to the introduction of a huge number of adjustable and interdependent system parameters (e.g., routing configurations, modulation format, symbol rate, coding schemes, etc.) that are enabled by the usage of coherent transmission/reception technologies, advanced digital signal processing and compensation of nonlinear effects in optical fiber propagation. In this paper we provide an overview of the application of ML to optical communications and networking. We classify and survey relevant literature dealing with the topic, and we also provide an introductory tutorial on ML for researchers and practitioners interested in this field. Although a good number of research papers have recently appeared, the application of ML to optical networks is still in its infancy: to stimulate further work in this area, we conclude the paper proposing new possible research directions