MetExplore: a web server to link metabolomic experiments and genome-scale metabolic networks

High-throughput metabolomic experiments aim at identifying and ultimately quantifying all metabolites present in biological systems. The metabolites are interconnected through metabolic reactions, generally grouped into metabolic pathways. Classical metabolic maps provide a relational context to help interpret metabolomics experiments and a wide range of tools have been developed to help place metabolites within metabolic pathways. However, the representation of metabolites within separate disconnected pathways overlooks most of the connectivity of the metabolome. By definition, reference pathways cannot integrate novel pathways nor show relationships between metabolites that may be linked by common neighbours without being considered as joint members of a classical biochemical pathway. MetExplore is a web server that offers the possibility to link metabolites identified in untargeted metabolomics experiments within the context of genome-scale reconstructed metabolic networks. The analysis pipeline comprises mapping metabolomics data onto the specific metabolic network of an organism, then applying graph-based methods and advanced visualization tools to enhance data analysis. The MetExplore web server is freely accessible at http://metexplore.toulouse.inra.fr.

[1]  Peter D. Karp,et al.  MetaCyc and AraCyc. Metabolic Pathway Databases for Plant Research1[w] , 2005, Plant Physiology.

[2]  Carol J Bult,et al.  MouseCyc: a curated biochemical pathways database for the laboratory mouse , 2009, Genome Biology.

[3]  Oliver Ebenhöh,et al.  An environmental perspective on metabolism. , 2008, Journal of theoretical biology.

[4]  Susumu Goto,et al.  KEGG for representation and analysis of molecular networks involving diseases and drugs , 2009, Nucleic Acids Res..

[5]  A Finney,et al.  Systems biology markup language: Level 2 and beyond. , 2003, Biochemical Society transactions.

[6]  Oliver Fiehn,et al.  Metabolomic database annotations via query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm , 2006, BMC Bioinformatics.

[7]  Karsten Suhre,et al.  MassTRIX: mass translator into pathways , 2008, Nucleic Acids Res..

[8]  Ferenc Jordán,et al.  A network perspective on the topological importance of enzymes and their phylogenetic conservation , 2007, BMC Bioinformatics.

[9]  Peter D. Karp,et al.  A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases , 2004, BMC Bioinformatics.

[10]  M. Tomita,et al.  Pathway Projector: Web-Based Zoomable Pathway Browser Using KEGG Atlas and Google Maps API , 2009, PloS one.

[11]  Oliver Fiehn,et al.  Combining Genomics, Metabolome Analysis, and Biochemical Modelling to Understand Metabolic Networks , 2001, Comparative and functional genomics.

[12]  C. Médigue,et al.  MaGe: a microbial genome annotation system supported by synteny results , 2006, Nucleic acids research.

[13]  Suzanne M. Paley,et al.  The Pathway Tools cellular overview diagram and Omics Viewer , 2006, Nucleic acids research.

[14]  Laurent Debrauwer,et al.  Use of reconstituted metabolic networks to assist in metabolomic data visualization and mining , 2010, Metabolomics.

[15]  M. Kimmel,et al.  Conflict of interest statement. None declared. , 2010 .

[16]  P. Karp,et al.  Computational prediction of human metabolic pathways from the complete human genome , 2004, Genome Biology.

[17]  H. Ginsburg.  Caveat emptor: limitations of the automated reconstruction of metabolic pathways in Plasmodium. , 2009, Trends in parasitology.

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

[19]  Peter D. Karp,et al.  EcoCyc: A comprehensive view of Escherichia coli biology , 2008, Nucleic Acids Res..

[20]  Oliver Ebenhöh,et al.  Expanding Metabolic Networks: Scopes of Compounds, Robustness, and Evolution , 2005, Journal of Molecular Evolution.

[21]  David S. Wishart,et al.  HMDB: a knowledgebase for the human metabolome , 2008, Nucleic Acids Res..

[22]  Peer Bork,et al.  KEGG Atlas mapping for global analysis of metabolic pathways , 2008, Nucleic Acids Res..

[23]  V. Lacroix,et al.  An Introduction to Metabolic Networks and Their Structural Analysis , 2008, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[24]  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.

[25]  R. Altman,et al.  Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery. , 2004, Genome research.

[26]  C. Francke,et al.  Reconstructing the metabolic network of a bacterium from its genome. , 2005, Trends in microbiology.