The mEPN scheme: an intuitive and flexible graphical system for rendering biological pathways

BackgroundThere is general agreement amongst biologists about the need for good pathway diagrams and a need to formalize the way biological pathways are depicted. However, implementing and agreeing how best to do this is currently the subject of some debate.ResultsThe modified Edinburgh Pathway Notation (mEPN) scheme is founded on a notation system originally devised a number of years ago and through use has now been refined extensively. This process has been primarily driven by the author's attempts to produce process diagrams for a diverse range of biological pathways, particularly with respect to immune signaling in mammals. Here we provide a specification of the mEPN notation, its symbols, rules for its use and a comparison to the proposed Systems Biology Graphical Notation (SBGN) scheme.ConclusionsWe hope this work will contribute to the on-going community effort to develop a standard for depicting pathways and will provide a coherent guide to those planning to construct pathway diagrams of their biological systems of interest.

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

[2]  R. Iyengar,et al.  Modeling cell signaling networks. , 2004, Biology of the cell.

[3]  Stijn van Dongen,et al.  Construction, Visualisation, and Clustering of Transcription Networks from Microarray Expression Data , 2007, PLoS Comput. Biol..

[4]  Imre Vastrik,et al.  Reactome: a knowledgebase of biological pathways , 2004, OTM Workshops.

[5]  K. Schroder,et al.  Interferon- : an overview of signals, mechanisms and functions , 2004 .

[6]  Gary D. Bader,et al.  Pathguide: a Pathway Resource List , 2005, Nucleic Acids Res..

[7]  Anton J. Enright,et al.  A logic-based diagram of signalling pathways central to macrophage activation , 2008, BMC Systems Biology.

[8]  S. Akira,et al.  Structure and function of a new STAT-induced STAT inhibitor , 1997, Nature.

[9]  Sarala M. Wimalaratne,et al.  The Systems Biology Graphical Notation , 2009, Nature Biotechnology.

[10]  A. Verma,et al.  Protein kinase C-delta (PKC-delta ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. , 2002, The Journal of biological chemistry.

[11]  Luay Nakhleh,et al.  The Signaling Petri Net-Based Simulator: A Non-Parametric Strategy for Characterizing the Dynamics of Cell-Specific Signaling Networks , 2008, PLoS Comput. Biol..

[12]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..

[13]  G. Stark,et al.  Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-& gamma; signal transduction pathway , 1993, Nature.

[14]  H. Ozer,et al.  Identification of the T cell subset that produces human gamma interferon. , 1982, Journal of Immunology.

[15]  Warren S. Alexander,et al.  Suppressors of cytokine signalling (SOCS) in the immune system , 2002, Nature Reviews Immunology.

[16]  Anushya Muruganujan,et al.  PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification , 2003, Nucleic Acids Res..

[17]  W. Windsor,et al.  Crystal structure of a complex between interferon-γ and its soluble high-affinity receptor , 1995, Nature.

[18]  J. Weinstein,et al.  Molecular interaction maps of bioregulatory networks: a general rubric for systems biology. , 2005, Molecular biology of the cell.

[19]  A. Larner,et al.  The Jak kinases differentially associate with the alpha and beta (accessory factor) chains of the interferon gamma receptor to form a functional receptor unit capable of activating STAT transcription factors. , 1995, The Journal of biological chemistry.

[20]  Gopal R. Gopinath,et al.  Correction: Reactome: a knowledge base of biologic pathways and processes , 2009, Genome Biology.

[21]  E. Barillot,et al.  A comprehensive modular map of molecular interactions in RB/E2F pathway , 2008, Molecular systems biology.

[22]  M. Kwiatkowska,et al.  Biological pathways as communicating computer systems , 2009, Journal of Cell Science.

[23]  Alexander R. Pico,et al.  WikiPathways: Pathway Editing for the People , 2008, PLoS biology.

[24]  K. Kohn.  Molecular interaction map of the mammalian cell cycle control and DNA repair systems. , 1999, Molecular biology of the cell.

[25]  BMC Systems Biology , 2007 .

[26]  Ian M. Donaldson,et al.  The Biomolecular Interaction Network Database and related tools 2005 update , 2004, Nucleic Acids Res..

[27]  Igor Goryanin,et al.  A Graphical Notation to describe the Logical Interactions of Biological Pathways , 2006, J. Integr. Bioinform..

[28]  Takaho A. Endo,et al.  A new protein containing an SH2 domain that inhibits JAK kinases , 1997, Nature.

[29]  Yukiko Matsuoka,et al.  Using process diagrams for the graphical representation of biological networks , 2005, Nature Biotechnology.

[30]  M. Tremblay,et al.  The T Cell Protein Tyrosine Phosphatase Is a Negative Regulator of Janus Family Kinases 1 and 3 , 2002, Current Biology.

[31]  M. Akagi,et al.  Induction of interferon-gamma production by human natural killer cells stimulated by hydrogen peroxide. , 1985, Journal of immunology.

[32]  P. Krammer,et al.  Production of immune interferon by murine T-cell clones from long-term cultures , 1981, Nature.

[33]  A. Wilks,et al.  Interferon-gamma induces tyrosine phosphorylation of interferon-gamma receptor and regulated association of protein tyrosine kinases, Jak1 and Jak2, with its receptor. , 1994, The Journal of biological chemistry.

[34]  P. Jensen,et al.  Transcriptional regulation of the MHC class II antigen presentation pathway. , 2003, Current opinion in immunology.

[35]  D. White,et al.  Rel/NF-kappaB/IkappaB proteins and cancer. , 1996, Oncogene.

[36]  W. Windsor,et al.  Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor. , 1995, Nature.

[37]  Falk Schreiber,et al.  Kinetic Modelling with the Systems Biology Modelling Environment SyBME , 2006, J. Integr. Bioinform..

[38]  W. Reith,et al.  Regulation of MHC class II gene expression by the class II transactivator , 2005, Nature Reviews Immunology.

[39]  Anton J. Enright,et al.  Network visualization and analysis of gene expression data using BioLayout Express3D , 2009, Nature Protocols.

[40]  H. Kitano,et al.  A comprehensive map of the toll-like receptor signaling network , 2006, Molecular systems biology.

[41]  Kenneth H. Buetow,et al.  PID: the Pathway Interaction Database , 2008, Nucleic Acids Res..

[42]  H. Kitano,et al.  A comprehensive pathway map of epidermal growth factor receptor signaling , 2005, Molecular systems biology.

[43]  J. ten Hoeve,et al.  Identification of a Nuclear Stat1 Protein Tyrosine Phosphatase , 2002, Molecular and Cellular Biology.

[44]  A. Verma,et al.  Protein Kinase C-δ (PKC-δ) Is Activated by Type I Interferons and Mediates Phosphorylation of Stat1 on Serine 727* , 2002, The Journal of Biological Chemistry.

[45]  K. Schroder,et al.  Interferon-gamma: an overview of signals, mechanisms and functions. , 2004, Journal of leukocyte biology.

[46]  Lincoln Stein,et al.  Reactome: a knowledgebase of biological pathways , 2004, Nucleic Acids Res..

[47]  Yoshihiro Yamanishi,et al.  KEGG for linking genomes to life and the environment , 2007, Nucleic Acids Res..

[48]  Allan Kuchinsky,et al.  Exploring Biological Networks with Cytoscape Software , 2008, Current protocols in bioinformatics.

[49]  Ying Chen,et al.  Construction of a large scale integrated map of macrophage pathogen recognition and effector systems , 2010, BMC Systems Biology.