114,952 research outputs found
Structure and parameter estimation for cell systems biology models
In this work we present a new methodology for structure and parameter estimation in cell systems biology modelling. Our modelling framework is based on P systems, an unconventional computational paradigm that abstracts from the structure and functioning of the living cell. The process of designing models, consisting of both the optimisation of the modular structure and of the stochastic kinetic parameters, is performed using a memetic algorithm. Specically, we use a nested evolutionary algorithm where the first layer evolves rule structures while the inner layer, implemented also as a genetic algorithm (GA), fine tunes the parameters of the model. Our approach consists of an incremental methodology. Starting from very simple P system modules specifying basic molecular interactions, more complicated modules are produced to model more complex molecular systems. These newly found modules are in turn added to the library of available P systems modules so as to be used subsequently to develop more intricate and circuitous cellular models. The effectiveness of the algorithm was tested on three case studies, namely, molecular complexation, enzymatic reactions and autoregulation in transcriptional networks.Kingdom's Engineering and Physical Sciences Research Council EP/ E017215/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/F01855X/
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
Numerical algebraic geometry for model selection and its application to the life sciences
Researchers working with mathematical models are often confronted by the
related problems of parameter estimation, model validation, and model
selection. These are all optimization problems, well-known to be challenging
due to non-linearity, non-convexity and multiple local optima. Furthermore, the
challenges are compounded when only partial data is available. Here, we
consider polynomial models (e.g., mass-action chemical reaction networks at
steady state) and describe a framework for their analysis based on optimization
using numerical algebraic geometry. Specifically, we use probability-one
polynomial homotopy continuation methods to compute all critical points of the
objective function, then filter to recover the global optima. Our approach
exploits the geometric structures relating models and data, and we demonstrate
its utility on examples from cell signaling, synthetic biology, and
epidemiology.Comment: References added, additional clarification
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
Training deep neural density estimators to identify mechanistic models of neural dynamics
Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators-- trained using model simulations-- to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features, and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin-Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics
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