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

Multi-membership gene regulation in pathway based microarray analysis

This article is available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. Results: We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. Conclusions: We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes.The work was sponsored by the studentship scheme of the School of Information Systems, Computing and Mathematics, Brunel Universit

Modeling, Simulating, and Parameter Fitting of Biochemical Kinetic Experiments

In many chemical and biological applications, systems of differential equations containing unknown parameters are used to explain empirical observations and experimental data. The DEs are typically nonlinear and difficult to analyze, requiring numerical methods to approximate the solutions. Compounding this difficulty are the unknown parameters in the DE system, which must be given specific numerical values in order for simulations to be run. Estrogen receptor protein dimerization is used as an example to demonstrate model construction, reduction, simulation, and parameter estimation. Mathematical, computational, and statistical methods are applied to empirical data to deduce kinetic parameter estimates and guide decisions regarding future experiments and modeling. The process demonstrated serves as a pedagogical example of quantitative methods being used to extract parameter values from biochemical data models.Comment: 23 pages, 9 figures, to be published in SIAM Revie

Extending fragment-based free energy calculations with library Monte Carlo simulation: Annealing in interaction space

Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via "library-based Monte Carlo") and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all-atom poly-alanine systems in a simple dielectric "solvent" and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor is required. The combined approach is formally equivalent to the "annealed importance sampling" algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is "grown." We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site