Standards and Tools for Model Exchange and Analysis in Systems Biology

This work is about standards in systems biology and about support for these standards in systems biology software tools. The work is divided into three sections. The first section describes an extension to the systems biology markup language (SBML) for the storage of graphical information on biochemical reaction networks. In the first part it explains the history of the extension, what it is about and what it can be used for and in the second part it details implementations of the extension in the form of several different software tools. The second section of this work deals with the Systems Biology Markup Language (SBML) standard and the different aspects of its support in the COPASI software tool. COPASI is a tool for the simulation and analysis of biochemical reaction networks and it uses SBML files as an exchange format for these reaction network models. This section highlights the different aspects of the implementation of the SBML standard as well as the extension to the SBML standard that is described in the first section of this work. Additionally this section describes how the functionality of COPASI, which is written in the C++ programming language, has been made available to developers using other programming languages like Java or Python and how this functionality is used in different systems biology computer programs around the world. The third section of this thesis discusses methods for the normalization and comparison of mathematical expressions and the implementation of these methods in the form of a computer program. This program is used to analyze the mathematical expressions in all models of the current release of the BioModels database. At several occasions in this text, it is demonstrated how the methods and tools described in these three sections can make a valuable contribution to research in systems biology.

[1]  Markus J. Herrgård,et al.  A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology , 2008, Nature Biotechnology.

[2]  N. Goodman.  Biological data becomes computer literate: new advances in bioinformatics. , 2002, Current opinion in biotechnology.

[3]  Lei Zhang,et al.  Hippo signaling pathway and organ size control , 2009, Fly.

[4]  Darren J. Wilkinson,et al.  The SBML discrete stochastic models test suite , 2008, Bioinform..

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

[6]  Bruce E. Shapiro,et al.  MathSBML: a package for manipulating SBML-based biological models , 2004, Bioinform..

[7]  Hugh D. Spence,et al.  Minimum information requested in the annotation of biochemical models (MIRIAM) , 2005, Nature Biotechnology.

[8]  F. Bruggeman,et al.  The nature of systems biology. , 2007, Trends in microbiology.

[9]  M A Aon,et al.  CHAOTIC DYNAMICS AND FRACTAL SPACE IN BIOCHEMISTRY: SIMPLICITY UNDERLIES COMPLEXITY , 2000, Cell biology international.

[10]  Michael Darsow,et al.  ChEBI: a database and ontology for chemical entities of biological interest , 2007, Nucleic Acids Res..

[11]  F. Crick.  Central Dogma of Molecular Biology , 1970, Nature.

[12]  Pedro Mendes,et al.  GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems , 1993, Comput. Appl. Biosci..

[13]  Pauline C Ng,et al.  Whole genome sequencing. , 2010, Methods in molecular biology.

[14]  Lincoln Stein,et al.  Reactome: a database of reactions, pathways and biological processes , 2010, Nucleic Acids Res..

[15]  B. G. Olivier,et al.  Modelling Cellular Processes With Python and Scipy , 2004, Molecular Biology Reports.

[16]  N. Fausto,et al.  New concepts in liver regeneration , 2011, Journal of gastroenterology and hepatology.

[17]  Kirill Degtyarenko,et al.  ChEBI: An Open Bioinformatics and Cheminformatics Resource , 2009, Current protocols in bioinformatics.

[18]  U Rost,et al.  Visualisation of biochemical network simulations with SimWiz. , 2004, Systems biology.

[19]  U. Bhalla,et al.  Emergent properties of networks of biological signaling pathways. , 1999, Science.

[20]  R. Kinne,et al.  Vitalism and Synthesis of Urea , 1999, American Journal of Nephrology.

[21]  Marvin Cassman,et al.  Barriers to progress in systems biology , 2005, Nature.

[22]  G. Michalopoulos.  Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. , 2010, The American journal of pathology.

[23]  Adam P. Arkin,et al.  Complex Systems: From chemistry to systems biology , 2009, Proceedings of the National Academy of Sciences.

[24]  H. Kitano,et al.  Computational systems biology , 2002, Nature.

[25]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[26]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[27]  Edda Klipp,et al.  TIde: a software for the systematic scanning of drug targets in kinetic network models , 2009, BMC Bioinformatics.

[28]  Herbert M. Sauro,et al.  Bioinformatics Applications Note Comparing Simulation Results of Sbml Capable Simulators , 2022 .

[29]  Kent L. Beck,et al.  Test-driven Development - by example , 2002, The Addison-Wesley signature series.

[30]  Khorana Hg.  Polynucleotide synthesis and the genetic code. , 1965 .

[31]  Matthew R. Pocock,et al.  The Bioperl toolkit: Perl modules for the life sciences. , 2002, Genome research.

[32]  Andreas Zell,et al.  SBMLsqueezer: A CellDesigner plug-in to generate kinetic rate equations for biochemical networks , 2008, BMC Systems Biology.

[33]  Mudita Singhal,et al.  COPASI - a COmplex PAthway SImulator , 2006, Bioinform..

[34]  Kei-Hoi Cheung,et al.  BioPAX – A community standard for pathway data sharing , 2010, Nature Biotechnology.

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

[36]  Edda Klipp,et al.  Annotation and merging of SBML models with semanticSBML , 2010, Bioinform..

[37]  Herbert M. Sauro,et al.  SBML2TikZ: supporting the SBML render extension in LaTeX , 2010, Bioinform..

[38]  G. Halder,et al.  Hippo signaling: growth control and beyond , 2011, Development.

[39]  Jacky L. Snoep,et al.  BioModels Database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems , 2005, Nucleic Acids Res..

[40]  S. Schuster,et al.  The modelling of metabolic systems. Structure, control and optimality. , 1998, Bio Systems.

[41]  Bartek Wilczynski,et al.  Biopython: freely available Python tools for computational molecular biology and bioinformatics , 2009, Bioinform..

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

[43]  Catherine M Lloyd,et al.  CellML: its future, present and past. , 2004, Progress in biophysics and molecular biology.

[44]  R. Heinrich,et al.  Metabolic Pathway Analysis: Basic Concepts and Scientific Applications in the Post‐genomic Era , 1999, Biotechnology progress.

[45]  D. Pan,et al.  Hippo signaling in organ size control. , 2007, Genes & development.

[46]  R. Dahm.  Discovering DNA: Friedrich Miescher and the early years of nucleic acid research , 2007, Human Genetics.

[47]  Steve Pettifer,et al.  Arcadia: a visualization tool for metabolic pathways , 2010, Bioinform..

[48]  B. Edgar,et al.  Filling out the Hippo pathway , 2007, Nature Reviews Molecular Cell Biology.

[49]  Melanie I. Stefan,et al.  BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models , 2010, BMC Systems Biology.

[50]  Stefanie Widder,et al.  The SBML ODE Solver Library: a native API for symbolic and fast numerical analysis of reaction networks , 2006, Bioinform..

[51]  F. Crick,et al.  Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid , 1953, Nature.

[52]  Herbert M. Sauro,et al.  Supporting the SBML layout extension , 2006, Bioinform..

[53]  Hiroaki Kitano,et al.  Next generation simulation tools: the Systems Biology Workbench and BioSPICE integration. , 2003, Omics : a journal of integrative biology.

[54]  A. Casadevall,et al.  Reductionistic and Holistic Science , 2011, Infection and Immunity.

[55]  F. Sanger,et al.  Nucleotide sequence of bacteriophage φX174 DNA , 1977, Nature.

[56]  J. Kountouras,et al.  Liver regeneration after hepatectomy. , 2001, Hepato-gastroenterology.

[57]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

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

[59]  Rodrigo Weber dos Santos,et al.  CellML and associated tools and techniques , 2008, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[60]  T. Ideker,et al.  A new approach to decoding life: systems biology. , 2001, Annual review of genomics and human genetics.