Standards and languages in Computational System Biology

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Standards and languages in Computational System
Biology
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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 computational model exchange
• BioPAX language for database of biological
  networks exchange
• SBGN visual language for biological model
  description

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Standard

• Scope of interest
• Language
• Controlled vocabulary

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SBML

• The Systems Biology Markup Language (SBML) is a
  computer-readable format for representing models
  of biochemical reaction networks. SBML is
  applicable to metabolic networks, cell-signaling
  pathways, regulatory networks, and many others.

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SBML

• Reaction
• container for rate law
• Species
• reactants, products, or modifiers of reaction
• Compartment
• container for species
• Parameter, Rule, Event

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Characteristics of SBML

• Many top-level types, little nesting
• Units, Compartment, Species, Parameter, Reaction,
  Rule, Function, Event
• Non-modular structure
• Next SBML Level (3) will introduce modularity
• Emphasis on reactions
• Some math implicit
• Explicit rate equations implicit integration
• Implicit concentration conversion between
  compartments
• Compartments are physical containers for species
• Spatial dimensions (volume, surface)

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Structure of SBML
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Structure of SBML

• Note field of SBase intended to store information
  for human to read
• Annotation field of SBase provide a container for
  software-generated annotations that are not
  intended to be seen by humans
• The id field is usually required for most
  structures and is used to identify a component
  within the model definition.
• The name field is optional and provide a
  human-readable label for the component.

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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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SBGN

• The international SBGN project aims to bring
  consistency and uniformity to the graphical
  expression of network diagrams in biology, in the
  same way that electronic circuit diagrams are
  standardized in electrical engineering.

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SBGN diagrams

• Process diagram visualise state transitions in
  the biological system
• Entity Relation diagram visualise possible
  interactions between elements of the system

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SBGN proposals

• Process diagram Kitano notation

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SBGN proposals

• ER diagram -MIM

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SBGN proposal

• Edinburgh hierarchical notation you are using
  for your assignment

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Kitano notation
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Kitano notation
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Kitano notation
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Kitano notation
Example of Process DiagramG-protein
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MIM

• Each molecule appears only once per diagram.
• Interaction outcomes - complexes or modified
  molecules - are depicted as nodes on the
  interaction lines.

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MIM
P
P PO4, a phosphate group
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MIM
Activating phosphorylation The phosphorylated
form of kinase A is the active form,
phosphorylates B
P
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MIM

• An Explicit MIM Depicts Molecular Interactions
  With Sufficient Detail Required for Simulation
• Heuristic MIMs concisely depict complex networks
  of molecular interactions

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EPE SBML creation

• Property for Species ID
• Property for Reaction ID
• Property for Compartment ID
• Property for Species Name
• Property for Reaction Name
• Property for Compartment Name

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References

• www.sbml.org
• www.biopax.org
• www.sbgn.org