Reaction Motifs in Metabolic Networks

The classic view of metabolism as a collection of metabolic pathways is being questioned with the currently available possibility of studying whole networks. Novel ways of decomposing the network into modules and motifs that could be considered as the building blocks of a network are being suggested. In this work, we introduce a new definition of motif in the context of metabolic networks. Unlike in previous works on (other) biochemical networks, this definition is not based only on topological features. We propose instead to use an alternative definition based on the functional nature of the components that form the motif. After introducing a formal framework motivated by biological considerations, we present complexity results on the problem of searching for all occurrences of a reaction motif in a network, and introduce an algorithm that is fast in practice in most situations. We then show an initial application to the study of pathway evolution.

[1]  A. Arkin,et al.  Motifs, modules and games in bacteria. , 2003, Current opinion in microbiology.

[2]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[3]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[4]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[5]  A. Lazcano,et al.  Molecular Evolution of the Lysine Biosynthetic Pathways , 2002, Journal of Molecular Evolution.

[6]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[7]  R. Albert,et al.  The large-scale organization of metabolic networks , 2000, Nature.

[8]  J. Stelling Mathematical models in microbial systems biology. , 2004, Current opinion in microbiology.

[9]  Monika Heiner,et al.  Steady state analysis of metabolic pathways using Petri nets , 2003, Silico Biol..

[10]  R. Guimerà,et al.  Functional cartography of complex metabolic networks , 2005, Nature.

[11]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[12]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[13]  Masanori Arita The metabolic world of Escherichia coli is not small. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  David S. Johnson,et al.  Computers and Intractability: A Guide to the Theory of NP-Completeness , 1978 .

[15]  Daniel Segrè,et al.  The regulatory software of cellular metabolism. , 2004, Trends in biotechnology.

[16]  An-Ping Zeng,et al.  Decomposition of metabolic network into functional modules based on the global connectivity structure of reaction graph , 2004, Bioinform..

[17]  Hideo Matsuda,et al.  A Multiple Alignment Algorithm for Metabolic Pathway Analysis Using Enzyme Hierarchy , 2000, ISMB.

[18]  Jason A. Papin,et al.  Comparison of network-based pathway analysis methods. , 2004, Trends in biotechnology.

[19]  Bernhard O Palsson,et al.  Hierarchical thinking in network biology: the unbiased modularization of biochemical networks. , 2004, Trends in biochemical sciences.

[20]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..

[21]  Thomas Pfeiffer,et al.  Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae , 2002, Bioinform..