21 research outputs found

    Bigraphical models for protein and membrane interactions

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    We present a bigraphical framework suited for modeling biological systems both at protein level and at membrane level. We characterize formally bigraphs corresponding to biologically meaningful systems, and bigraphic rewriting rules representing biologically admissible interactions. At the protein level, these bigraphic reactive systems correspond exactly to systems of kappa-calculus. Membrane-level interactions are represented by just two general rules, whose application can be triggered by protein-level interactions in a well-de\"ined and precise way. This framework can be used to compare and merge models at different abstraction levels; in particular, higher-level (e.g. mobility) activities can be given a formal biological justification in terms of low-level (i.e., protein) interactions. As examples, we formalize in our framework the vesiculation and the phagocytosis processes

    Programmable models of growth and mutation of cancer-cell populations

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    In this paper we propose a systematic approach to construct mathematical models describing populations of cancer-cells at different stages of disease development. The methodology we propose is based on stochastic Concurrent Constraint Programming, a flexible stochastic modelling language. The methodology is tested on (and partially motivated by) the study of prostate cancer. In particular, we prove how our method is suitable to systematically reconstruct different mathematical models of prostate cancer growth - together with interactions with different kinds of hormone therapy - at different levels of refinement.Comment: In Proceedings CompMod 2011, arXiv:1109.104

    External Control in Process Algebra for Systems Biology

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    A critical aspect in the modeling of biological systems is the description view point. On the one hand, the Stochastic \u3c0-calculus formalism provides an intuitive and compact representation from an internal perspective. On the other hand, other proposed languages such as Hybrid Automata and Stochastic Concurrent Constraint Programming introduce in the system description an external control and provide more structured models. This work aims at bridging the above discussed gap. In particular, we propose a different approach for the encoding of biological systems in Stochastic \u3c0-calculus in the direction of introducing an external control and comparing different formalisms. We show the effectiveness of our method on some examples

    Biocharts: a visual formalism for complex biological systems

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    We address one of the central issues in devising languages, methods and tools for the modelling and analysis of complex biological systems, that of linking high-level (e.g. intercellular) information with lower-level (e.g. intracellular) information. Adequate ways of dealing with this issue are crucial for understanding biological networks and pathways, which typically contain huge amounts of data that continue to grow as our knowledge and understanding of a system increases. Trying to comprehend such data using the standard methods currently in use is often virtually impossible. We propose a two-tier compound visual language, which we call Biocharts, that is geared towards building fully executable models of biological systems. One of the main goals of our approach is to enable biologists to actively participate in the computational modelling effort, in a natural way. The high-level part of our language is a version of statecharts, which have been shown to be extremely successful in software and systems engineering. The statecharts can be combined with any appropriately well-defined language (preferably a diagrammatic one) for specifying the low-level dynamics of the pathways and networks. We illustrate the language and our general modelling approach using the well-studied process of bacterial chemotaxis

    A Software Interface Between the Narrative Language and Bio-PEPA

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    AbstractWe present a software tool for the automatic translation of models from the Narrative Language, a semi-formal language for biological modelling, into the Bio-PEPA process algebra. This provides biologists with an easy way to describe systems and at the same time gives them access to the simulation and analysis techniques provided by Bio-PEPA. We present details of the translation algorithm and its integration into existing software, and discuss ways in which this idea could be further explored

    Continuous approximation of collective system behaviour: A tutorial

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    In this paper we present an overview of the field of deterministic approximation of Markov processes, both in discrete and continuous times. We will discuss mean field approximation of discrete time Markov chains and fluid approximation of continuous time Markov chains, considering the cases in which the deterministic limit process lives in continuous time or discrete time. We also consider some more advanced results, especially those relating to the limit stationary behaviour. We assume a knowledge of modelling with Markov chains, but not of more advanced topics in stochastic processes

    Modeling and Simulation of Biological Systems through Electronic Design Automation techniques

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    Modeling and simulation of biological systems is a key requirement for integrating invitro and in-vivo experimental data. In-silico simulation allows testing different experimental conditions, thus helping in the discovery of the dynamics that regulate the system. These dynamics include errors in the cellular information processing that are responsible for diseases such as cancer, autoimmunity, and diabetes as well as drug effects to the system (Gonalves, 2013). In this context, modeling approaches can be classified into two categories: quantitative and qualitative models. Quantitative modeling allows for a natural representation of molecular and gene networks and provides the most precise prediction. Nevertheless, the lack of kinetic data (and of quantitative data in general) hampers its use for many situations (Le Novere, 2015). In contrast, qualitative models simplify the biological reality and are often able to reproduce the system behavior. They cannot describe actual concentration levels nor realistic time scales. As a consequence, they cannot be used to explain and predict the outcome of biological experiments that yield quantitative data. However, given a biological network consisting of input (e.g., receptors), intermediate, and output (e.g., transcription factors) signals, they allow studying the input-output relationships through discrete simulation (Samaga, 2013). Boolean models are gaining an increasing interest in reproducing dynamic behaviors, understanding processes, and predicting emerging properties of cellular signaling networks through in-silico experiments. They are emerging as a valid alternative to the quantitative approaches (i.e., based on ordinary differential equations) for exploratory modeling when little is known about reaction kinetics or equilibrium constants in the context of gene expression or signaling. Even though several approaches and software have been recently proposed for logic modeling of biological systems, they are limited to specific contexts and they lack of automation in analyzing biological properties such as complex attractors, and molecule vulnerability. This thesis proposes a platform based on Electronic Design Automation (EDA) technologies for qualitative modeling and simulation of Biological Systems. It aims at overtaking limitations that affect the most recent qualitative tools

    Computational Techniques for the Structural and Dynamic Analysis of Biological Networks

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    The analysis of biological systems involves the study of networks from different omics such as genomics, transcriptomics, metabolomics and proteomics. In general, the computational techniques used in the analysis of biological networks can be divided into those that perform (i) structural analysis, (ii) dynamic analysis of structural prop- erties and (iii) dynamic simulation. Structural analysis is related to the study of the topology or stoichiometry of the biological network such as important nodes of the net- work, network motifs and the analysis of the flux distribution within the network. Dy- namic analysis of structural properties, generally, takes advantage from the availability of interaction and expression datasets in order to analyze the structural properties of a biological network in different conditions or time points. Dynamic simulation is useful to study those changes of the biological system in time that cannot be derived from a structural analysis because it is required to have additional information on the dynamics of the system. This thesis addresses each of these topics proposing three computational techniques useful to study different types of biological networks in which the structural and dynamic analysis is crucial to answer to specific biological questions. In particu- lar, the thesis proposes computational techniques for the analysis of the network motifs of a biological network through the design of heuristics useful to efficiently solve the subgraph isomorphism problem, the construction of a new analysis workflow able to integrate interaction and expression datasets to extract information about the chromo- somal connectivity of miRNA-mRNA interaction networks and, finally, the design of a methodology that applies techniques coming from the Electronic Design Automation (EDA) field that allows the dynamic simulation of biochemical interaction networks and the parameter estimation
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