22066 articles – 15901 references  [version française]

inria-00538134, version 1

Designing Logical Rules to Model the Response of Biomolecular Networks with Complex Interactions: An Application to Cancer Modeling.

Carito Guziolowski a1, Sylvain Blachon 1, Tatiana Baumuratova, Gautier Stoll 2, Ovidiu Radulescu b13, Anne Siegel c1

IEEE/ACM Trans Comput Biol Bioinform 8, 5 (2011) 1223-1234

Abstract: We discuss the propagation of constraints in eukaryotic interaction networks in relation to model prediction and the identification of critical pathways. In order to cope with post-translational interactions we consider two types of nodes in the network, corresponding to proteins and to RNA. Micro-array data provides very lacunar information for such types of networks because protein nodes, although needed in the model, are not observed. Propagation of observations in such networks leads to poor and non-significant model predictions, mainly because rules used to propagate information -- usually disjunctive constraints -- are weak. Here we propose a new, stronger type of logical constraints that allow us to strengthen the analysis of the relation between micro-array and interaction data. We use these rules to identify which nodes are responsible for a phenotype, in particular for cell cycle progression. As the benchmark, we use an interaction network describing major pathways implied in the Ewing's tumor development. The Python library used to obtain our results is publicly available on our supplementary web page.

  • a –  INRIA
  • b –  Université de Rennes I
  • c –  CNRS
  • 1:  SYMBIOSE (INRIA - IRISA)
  • CNRS : UMR6074 – INRIA – Institut National des Sciences Appliquées (INSA) - Rennes – Université de Rennes 1
  • 2:  Service de Bioinformatique (CURIE-BIOINFO)
  • Institut Curie
  • 3:  Institut de Recherche Mathématique de Rennes (IRMAR)
  • CNRS : UMR6625 – Université de Rennes 1 – École normale supérieure de Cachan - ENS Cachan – Institut National des Sciences Appliquées (INSA) : - RENNES – Université de Rennes II - Haute Bretagne
  • Domain : Computer Science/Bioinformatics
    Life Sciences/Quantitative Methods
 
  • inria-00538134, version 1
  • oai:hal.inria.fr:inria-00538134
  • From: 
  • Submitted on: Sunday, 21 November 2010 17:58:47
  • Updated on: Friday, 11 November 2011 16:38:58