TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei

The metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individual metabolic networks is increasing as we learn more about the enzymes that are active in particular cells under particular conditions and as technologies advance to allow detailed measurements of the cellular metabolome. Metabolic network databases are of increasing importance in allowing us to contextualise data sets emerging from transcriptomic, proteomic and metabolomic experiments. Here we present a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describes the generic and condition-specific metabolic network of Trypanosoma brucei, a parasitic protozoan responsible for human and animal African trypanosomiasis. In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have also implemented a network-based representation of the information through MetExplore, yielding a novel environment in which to visualise the metabolism of this important parasite.

[1]  Malcolm J. McConville,et al.  LeishCyc: a biochemical pathways database for Leishmania major , 2009, BMC Systems Biology.

[2]  Michael P Barrett,et al.  Trypanosoma brucei: meet the system. , 2014, Current opinion in microbiology.

[3]  Intawat Nookaew,et al.  The RAVEN Toolbox and Its Use for Generating a Genome-scale Metabolic Model for Penicillium chrysogenum , 2013, PLoS Comput. Biol..

[4]  H. Ginsburg Progress in in silico functional genomics: the malaria Metabolic Pathways database. , 2006, Trends in parasitology.

[5]  Eileen Kraemer,et al.  TriTrypDB: a functional genomic resource for the Trypanosomatidae , 2009, Nucleic Acids Res..

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

[7]  Michael A. J. Ferguson,et al.  Comparative SILAC Proteomic Analysis of Trypanosoma brucei Bloodstream and Procyclic Lifecycle Stages , 2012, PloS one.

[8]  Peter D. Karp,et al.  EcoCyc: fusing model organism databases with systems biology , 2012, Nucleic Acids Res..

[9]  Vassilios Ioannidis,et al.  ExPASy: SIB bioinformatics resource portal , 2012, Nucleic Acids Res..

[10]  B. Chait,et al.  Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. , 1985, Science.

[11]  Rainer Breitling,et al.  Stable Isotope-Assisted Metabolomics for Network-Wide Metabolic Pathway Elucidation , 2012, Analytical chemistry.

[12]  The UniProt Consortium,et al.  Update on activities at the Universal Protein Resource (UniProt) in 2013 , 2012, Nucleic Acids Res..

[13]  J. Donelson,et al.  The Genome of the African Trypanosome , 2002 .

[14]  Michael P. Barrett,et al.  Untargeted Metabolomics Reveals a Lack Of Synergy between Nifurtimox and Eflornithine against Trypanosoma brucei , 2012, PLoS neglected tropical diseases.

[15]  Ines Thiele,et al.  Reconstruction annotation jamborees: a community approach to systems biology , 2010, Molecular systems biology.

[16]  Christoph Steinbeck,et al.  Metingear: a development environment for annotating genome-scale metabolic models , 2013, Bioinform..

[17]  María Martín,et al.  Activities at the Universal Protein Resource (UniProt) , 2013, Nucleic Acids Res..

[18]  F. Opperdoes,et al.  Particle-bound enzymes in the bloodstream form of Trypanosoma brucei. , 1977, European journal of biochemistry.

[19]  Ronan M. T. Fleming,et al.  Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0 , 2007, Nature Protocols.

[20]  Ronan M. T. Fleming,et al.  Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0 , 2007, Nature Protocols.

[21]  Michael P. Barrett,et al.  MetExplore: a web server to link metabolomic experiments and genome-scale metabolic networks , 2010, Nucleic Acids Res..

[22]  Ludovic Cottret,et al.  Graph methods for the investigation of metabolic networks in parasitology , 2010, Parasitology.

[23]  Michael Hippler,et al.  PredAlgo: a new subcellular localization prediction tool dedicated to green algae. , 2012, Molecular biology and evolution.

[24]  Ronan M. T. Fleming,et al.  A community-driven global reconstruction of human metabolism , 2013, Nature Biotechnology.

[25]  Ivica Letunic,et al.  metaTIGER: a metabolic evolution resource , 2008, Nucleic Acids Res..

[26]  Michael P Barrett,et al.  Potential new drugs for human African trypanosomiasis: some progress at last , 2010, Current opinion in infectious diseases.

[27]  David M. A. Martin,et al.  The Genome of the African Trypanosome Trypanosoma brucei , 2005, Science.

[28]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

[29]  Giuliano Cecchi,et al.  Human African trypanosomiasis , 2017, The Lancet.

[30]  John Gould,et al.  Toward the automated generation of genome-scale metabolic networks in the SEED , 2007, BMC Bioinformatics.

[31]  F. Bringaud,et al.  Metabolic aspects of glycosomes in trypanosomatidae - new data and views. , 2000, Parasitology today.

[32]  F. Opperdoes,et al.  Localization of nine glycolytic enzymes in a microbody‐like organelle in Trypanosoma brucei: The glycosome , 1977, FEBS letters.

[33]  M. Barrett,et al.  Determination of antiprotozoal drug mechanisms by metabolomics approaches , 2013, Parasitology.

[34]  Peter D. Karp,et al.  The Pathway Tools Pathway Prediction Algorithm , 2011, Standards in genomic sciences.

[35]  Michael L. Creech,et al.  Integration of biological networks and gene expression data using Cytoscape , 2007, Nature Protocols.

[36]  Antje Chang,et al.  BRENDA in 2013: integrated reactions, kinetic data, enzyme function data, improved disease classification: new options and contents in BRENDA , 2012, Nucleic Acids Res..

[37]  Haiming Wang,et al.  GeneDB—an annotation database for pathogens , 2011, Nucleic Acids Res..

[38]  Susumu Goto,et al.  Data, information, knowledge and principle: back to metabolism in KEGG , 2013, Nucleic Acids Res..

[39]  B. Berger,et al.  Aromatic amino acid transamination and methionine recycling in trypanosomatids. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

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

[41]  Antje Chang,et al.  BRENDA , the enzyme database : updates and major new developments , 2003 .

[42]  B. Palsson,et al.  A protocol for generating a high-quality genome-scale metabolic reconstruction , 2010 .

[43]  Andrew R. Jones,et al.  Library of Apicomplexan Metabolic Pathways: a manually curated database for metabolic pathways of apicomplexan parasites , 2012, Nucleic Acids Res..

[44]  Andrew G. McDonald,et al.  ExplorEnz: the primary source of the IUBMB enzyme list , 2008, Nucleic Acids Res..

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

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

[47]  Michael P Barrett,et al.  Proline Metabolism in Procyclic Trypanosoma brucei Is Down-regulated in the Presence of Glucose* , 2005, Journal of Biological Chemistry.

[48]  Jason A. Papin,et al.  Systems analysis of metabolism in the pathogenic trypanosomatid Leishmania major , 2008, Molecular systems biology.