Existing Standards in Systems Biology

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Existing Standards in Systems Biology
Anatoly Sorokin Computation Systems Biology
GroupUniversity of Edinburgh
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Standard

• Scope of interest
• Language
• Controlled vocabulary

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Standards and Languages

• CML description of chemical structure
• MathML representation of mathematical formulas
• PSI standard description of protein interaction
  data
• AnatML language to describe interaction at
  organ level
• GeneOntology standard and ontology to describe
  gene function and regulation

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Standards for Computational System Biology

• SBML language of biochemical model exchange
• CellML language to describe mathematical models
  
• BioPAX language for database of biological
  networks exchange
• SBGN visual language for biological model
  description

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BioPAX

• Biological PAthway eXchange - A data exchange
  ontology and format for biological pathway
  integration, aggregation and inference

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BioPAX / SBML
Database Exchange Formats
Simulation Model Exchange Formats
BioPAX
SBML, CellML
Genetic Interactions
PSI-MI 2
Rate Formulas
Biochemical Reactions
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BioPAX Goals

• BioPAX Biological PAthway eXchange
• Data exchange format for pathway data
• Include support for these pathway types
• Metabolic pathways
• Signaling pathways
• Protein-protein, molecular interactions
• Gene regulatory pathways
• Genetic interactions
• Accommodate representations used in existing
  databases such as BioCyc, BIND, WIT, aMAZE, KEGG,
  Reactome, etc.

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BioPAX

• BioPAX ontology and format in OWL (XML)
• Ontology built using GKB Editor and Protégé
• Semantic mapping still an issue
• Level 1 represents metabolic pathway data
• Level 2 adds support for molecular interactions,
  post-translational modifications, experimental
  description from PSI-MI model (Backwards
  compatible)

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BioPAX Ontology Overview
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BioPAX Ontology Top Level

• Pathway
• A set of interactions
• E.g. Glycolysis, MAPK, Apoptosis
• Interaction
• A set of entities and some relationship between
  them
• E.g. Reaction, Molecular Association, Catalysis
• Physical Entity
• A building block of simple interactions
• E.g. Small molecule, Protein, DNA, RNA

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BioPAX Ontology Interactions
Interaction
Physical Interaction
Control
Conversion
ComplexAssembly
Catalysis
BiochemicalReaction
Modulation
Transport
TransportWithBiochemicalReaction
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BioPAX Ontology Physical Entities
PhysicalEntity
Complex
RNA
Protein
Small Molecule
DNA
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BioPAX future directions

• Level 3
• Molecular states
• Generic
• Gene regulation

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MinimalRequirements



implements
implements
Data model



Makes sense of
Makes sense of
Ontology
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SBML

• Exchange language for biochemical models
• Small number of key components
• Compartment
• Specie (pool of molecules)
• Reaction
• Support for mathematical formulations
• Rate law
• Rules
• Events

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MIRIAM

• Model description require extra information
• Biological
• Description of elements of model
• Mathematical
• Definition of math concepts
• Referential
• Author name
• Paper reference etc.
• http//www.ebi.ac.uk/compneur-srv/miriam/

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Reference correspondence

• The model must be encoded in a public,
  standardized, machine-readable format (SBML,
  CellML, GENESIS ...)
• The model must comply with the standard in which
  it is encoded!
• The model must be clearly related to a single
  reference description. If a model is composed
  from different parts, there should still be a
  description of the derived/combined model.
• The encoded model structure must reflect the
  biological processes listed in the reference
  description.
• The model must be instantiated in a simulation
  All quantitative attributes have to be defined,
  including initial conditions.
• When instantiated, the model must be able to
  reproduce all results given in the reference
  description within an epsilon (algorithms,
  round-up errors)

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Attribution annotation

• The model has to be named.
• A citation of the reference description must be
  joined (completecitation, unique identifier,
  unambigous URL). The citation should permit to
  identify the authors of the model.
• The name and contact of model creators must be
  joined.
• The date and time of creation and last
  modification should be specified. An history is
  useful but not required.
• The model should be linked to a precise statement
  about the terms of distribution. MIRIAM does not
  require freedom of use or no cost.

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External resource annotation

• The annotation must permit to unambiguously
  relate a piece of knowledge to a model
  constituent.
• The referenced information should be described
  using a triplet data-type, identifier,
  qualifier
• The data-type should be written as a Unique
  Resource Identifier (URI)
• The identifier is analysed within the framework
  of the data-type.
• Data-type and Identifier can be combined in a
  single URI http//www.myResource.org/myIdentifie
  r urnlsidmyResource.orgmyIdentifier
• Qualifiers (optional) should refine the link
  between the model constitutent and the piece of
  knowledge has a, is version of, is homolog
  to etc.

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SBO

• Part of OBO Foundry
• Assign meanings to mathematical elements of SBML
• Allows automatic validation of semantic
  consistency of math part of model
• http//www.ebi.ac.uk/sbo

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SBO

• Types and roles of reaction participants,
  including terms like substrate, catalyst
  etc., but also macromolecule, or channel.
• Parameter used in quantitative models. This
  vocabulary includes terms like Michaelis
  constant , forward unimolecular rate
  constantetc. A term may contain a precise
  mathematical expression stored as a MathML lambda
  function. The variables refer to other
  parameters.
• Mathematical expressions. Examples of terms are
  mass action kinetics, Henri-Michaelis-Menten
  equation etc. A term may contain a precise
  mathematical expression stored as a MathML lambda
  function. The variables refer to the other
  vocabularies.
• Modelling framework to precise how to interpret
  the rate-law. E.g. continuous modelling,
  discrete modelling etc.
• Event type, such as catalysis or addition of a
  chemical group.

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SBO
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MIASE

• Minimum Information About a Simulation Experiment
• What base model to use which modifications to
  apply
• What simulation task to run on those models
  (algorithms, see KiSAO simulation parameters)
• How to post-process the numerical results and to
  present them
• http//www.ebi.ac.uk/compneur-srv/miase/
• Subset of MISE bould be encoded in SED-ML

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SED-ML

• Encode MIASE requirements

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Description of models
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Description of models
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Simulations
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Simulations
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Simulation task
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Data generation
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Data generation
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Production of results
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KiSAO

• Kinetic Simulation Algorithm Ontology
• Classification of simulation algorithms
  methods
• Definition, literature references
• Relations between different simulation algorithms
  methods
• http//www.ebi.ac.uk/compneur-srv/kisao/index.html

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KiSAO in OBO
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SBRML

• Systems Biology Results Markup Language
• A new markup language for specifying the results
  from operations on SBML models
• http//www.comp-sys-bio.org/tiki-index.php?pageSB
  RML

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SBRML
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Dimension example
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Dimension example
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TEDDY

• The TErminology for the Description of DYnamics
  (TEDDY) project aims to provide an ontology for
  dynamical behaviours, observable dynamical
  phenomena, and control elements of bio-models and
  biological systems in Systems Biology and
  Synthetic Biology.
• http//www.ebi.ac.uk/compneur-srv/teddy/

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TEDDY
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Access

• Web services
• MIRIAM URI resolution
• SBO
• KiSAO
• TEDDY
• Ontologies File formats
• OWL
• OBO