Modelling and analysis of structure in cellular signalling systems

QH301 Biology;QA75 Electronic computers. Computer science

Donaldson, Robin ; Calder, Muffy

University:University of Glasgow

Department:School of Computing Science

关键词: Signalling pathways, signalling networks, cross-talk, biological models, model checking, Markov chains, Petri nets;   

Others  :  http://theses.gla.ac.uk/3571/1/2012DonaldsonPhD.pdf

来源: University of Glasgow

【 摘 要 】

Cellular signalling is an important area of study in biology.Signalling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals.Collections of pathways form signalling networks, and interactions between pathways in a network, known as cross-talk, enables further complex signalling behaviours.Increasingly, computational modelling and analysis is required to handle the complexity of such systems.While there are several computational modelling approaches for signalling pathways, none make cross-talk explicit.We present a modular modelling framework for pathways and their cross-talk.Networks are formed by composing pathways: different cross-talks result from different synchronisations of reactions between, and overlaps of, the pathways.We formalise five types of cross-talk and give approaches to reason about possible cross-talks in a network.The complementary problem is how to handle unstructured signalling networks, i.e. networks with no explicit notion of pathways or cross-talk.We present an approach to better understand unstructured signalling networks by modelling them as a set of signal flows through the network.We introduce the Reaction Minimal Paths (RMP) algorithm that computes the set of signal flows in a model.To the best of our knowledge, current algorithms cannot guarantee both correctness and completeness of the set of signal flows in a model.The RMP algorithm is the first.Finally, the RMP algorithm suffers from the well-known state space explosion problem.We use suitable partial order reduction algorithms to improve the efficiency of this algorithm.