A framework for the integrated analysis of metabolic and regulatory networks

The analysis of cellular behavior and functionality is the most challenging aim of systems biology. The extensive analysis of the interactions between different classes of intra-cellular molecules reacting to genetic/environment changes can elucidate the mechanisms of regulation involved on different cellular processes. We propose a novel framework that enables the integrated analysis of metabolic and regulatory networks. The framework takes advantage on publicly available data repositories, sustaining the inference of knowledge from the integrated network. Since it is based on logic programming, it provides users with a powerful language to query information using both first and second order predicates. Also, it supports network topology analysis, motif finding and robustness evaluation. In this work, as an illustrative case study, our framework is used to build a model of the bacterium Escherichia coli K12.

[1]  Adam M. Feist,et al.  A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information , 2007, Molecular systems biology.

[2]  Susumu Goto,et al.  Regulation of metabolic networks by small molecule metabolites , 2007, BMC Bioinformatics.

[3]  Julio M. Ottino,et al.  Complex systems and networks: Challenges and opportunities for chemical and biological engineers , 2004 .

[4]  Jing Zhao,et al.  Complex networks theory for analyzing metabolic networks , 2006, q-bio/0603015.

[5]  S. Teichmann,et al.  Evolution of transcription factors and the gene regulatory network in Escherichia coli. , 2003, Nucleic acids research.

[6]  S. Strogatz.  Exploring complex networks , 2001, Nature.

[7]  B. Palsson,et al.  An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR) , 2003, Genome Biology.

[8]  Bas Teusink,et al.  Accelerating the reconstruction of genome-scale metabolic networks , 2006, BMC Bioinformatics.

[9]  Markus J. Herrgård,et al.  Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae. , 2006, Genome research.

[10]  Edward R. Dougherty,et al.  From Boolean to probabilistic Boolean networks as models of genetic regulatory networks , 2002, Proc. IEEE.

[11]  Albert-László Barabási,et al.  Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network , 2004, BMC Bioinformatics.

[12]  B. Palsson,et al.  Transcriptional regulation in constraints-based metabolic models of Escherichia coli Covert , 2002 .