Rule-Based Modelling and Model Perturbation

Vincent Danos, Jérôme Feret, Walter Fontana, Russ Harmer, Jean Krivine

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Rule-based modelling has already proved to be successful for taming the combinatorial complexity, typical of cellular signalling networks, caused by the combination of physical protein-protein interactions and modifications that generate astronomical numbers of distinct molecular species. However, traditional rule-based approaches, based on an unstructured space of agents and rules, remain susceptible to other combinatorial explosions caused by mutated and/or splice variant agents, that share most but not all of their rules with their wild-type counterparts; and by drugs, which must be clearly distinguished from physiological ligands.

In this paper, we define a syntactic extension of Kappa, an established rule-based modelling platform, that enables the expression of a structured space of agents and rules that allows us to express mutated agents, splice variants, families of related proteins and ligand/drug interventions uniformly. This also enables a mode of model construction where, starting from the current consensus model, we attempt to reproduce in numero the mutational—and more generally the ligand/drug perturbational—analyses that were used in the process of inferring those pathways in the first place.
Original languageEnglish
Title of host publicationTransactions on Computational Systems Biology XI
PublisherSpringer Berlin Heidelberg
Pages116-137
Number of pages22
Volume5750
ISBN (Electronic)978-3-642-04186-0
ISBN (Print)978-3-642-04185-3
DOIs
Publication statusPublished - 2009

Publication series

NameLecture Notes in Computer Science
PublisherSpringer Berlin Heidelberg
Volume5750
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

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