Parameter estimation for Boolean models of biological networks

Boolean networks have long been used as models of molecular networks and play an increasingly important role in systems biology. This paper describes a software package, Polynome, offered as a web service, that helps users construct Boolean network models based on experimental data and biological input. The key feature is a discrete analog of parameter estimation for continuous models. With only experimental data as input, the software can be used as a tool for reverse-engineering of Boolean network models from experimental time course data.Comment: Web interface of the software is available at http://polymath.vbi.vt.edu/polynome

Evolving stochastic learning algorithm based on Tsallis entropic index

In this paper, inspired from our previous algorithm, which was based on the theory of Tsallis statistical mechanics, we develop a new evolving stochastic learning algorithm for neural networks. The new algorithm combines deterministic and stochastic search steps by employing a different adaptive stepsize for each network weight, and applies a form of noise that is characterized by the nonextensive entropic index q, regulated by a weight decay term. The behavior of the learning algorithm can be made more stochastic or deterministic depending on the trade off between the temperature T and the q values. This is achieved by introducing a formula that defines a time-dependent relationship between these two important learning parameters. Our experimental study verifies that there are indeed improvements in the convergence speed of this new evolving stochastic learning algorithm, which makes learning faster than using the original Hybrid Learning Scheme (HLS). In addition, experiments are conducted to explore the influence of the entropic index q and temperature T on the convergence speed and stability of the proposed method

Mathematical modeling of genome replication

Peer reviewedPublisher PD

Optimization Algorithms for Computational Systems Biology

Computational systems biology aims at integrating biology and computational methods to gain a better understating of biological phenomena. It often requires the assistance of global optimization to adequately tune its tools. This review presents three powerful methodologies for global optimization that fit the requirements of most of the computational systems biology applications, such as model tuning and biomarker identification. We include the multi-start approach for least squares methods, mostly applied for fitting experimental data. We illustrate Markov Chain Monte Carlo methods, which are stochastic techniques here applied for fitting experimental data when a model involves stochastic equations or simulations. Finally, we present Genetic Algorithms, heuristic nature-inspired methods that are applied in a broad range of optimization applications, including the ones in systems biology

Global parameter estimation methods for stochastic biochemical systems

<p>Abstract</p> <p>Background</p> <p>The importance of stochasticity in cellular processes having low number of molecules has resulted in the development of stochastic models such as chemical master equation. As in other modelling frameworks, the accompanying rate constants are important for the end-applications like analyzing system properties (e.g. robustness) or predicting the effects of genetic perturbations. Prior knowledge of kinetic constants is usually limited and the model identification routine typically includes parameter estimation from experimental data. Although the subject of parameter estimation is well-established for deterministic models, it is not yet routine for the chemical master equation. In addition, recent advances in measurement technology have made the quantification of genetic substrates possible to single molecular levels. Thus, the purpose of this work is to develop practical and effective methods for estimating kinetic model parameters in the chemical master equation and other stochastic models from single cell and cell population experimental data.</p> <p>Results</p> <p>Three parameter estimation methods are proposed based on the maximum likelihood and density function distance, including probability and cumulative density functions. Since stochastic models such as chemical master equations are typically solved using a Monte Carlo approach in which only a finite number of Monte Carlo realizations are computationally practical, specific considerations are given to account for the effect of finite sampling in the histogram binning of the state density functions. Applications to three practical case studies showed that while maximum likelihood method can effectively handle low replicate measurements, the density function distance methods, particularly the cumulative density function distance estimation, are more robust in estimating the parameters with consistently higher accuracy, even for systems showing multimodality.</p> <p>Conclusions</p> <p>The parameter estimation methodologies described in this work have provided an effective and practical approach in the estimation of kinetic parameters of stochastic systems from either sparse or dense cell population data. Nevertheless, similar to kinetic parameter estimation in other modelling frameworks, not all parameters can be estimated accurately, which is a common problem arising from the lack of complete parameter identifiability from the available data.</p

Evolutionary Multiobjective Optimization Driven by Generative Adversarial Networks (GANs)

Recently, increasing works have proposed to drive evolutionary algorithms using machine learning models. Usually, the performance of such model based evolutionary algorithms is highly dependent on the training qualities of the adopted models. Since it usually requires a certain amount of data (i.e. the candidate solutions generated by the algorithms) for model training, the performance deteriorates rapidly with the increase of the problem scales, due to the curse of dimensionality. To address this issue, we propose a multi-objective evolutionary algorithm driven by the generative adversarial networks (GANs). At each generation of the proposed algorithm, the parent solutions are first classified into real and fake samples to train the GANs; then the offspring solutions are sampled by the trained GANs. Thanks to the powerful generative ability of the GANs, our proposed algorithm is capable of generating promising offspring solutions in high-dimensional decision space with limited training data. The proposed algorithm is tested on 10 benchmark problems with up to 200 decision variables. Experimental results on these test problems demonstrate the effectiveness of the proposed algorithm