Edinburgh Pathway Editor a flexible tool for biological model creation

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Edinburgh Pathway Editora flexible tool for
biological model creation

• Anatoly Sorokin
• Edinburgh Centre for Bioinformatics

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Edinburgh Pathway Editor
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Overall outline

• EPE introduction
• Installation
• LookFeel
• Basic operations
• Metabolic and math model creation
• EMP/WIT context
• Top/down approach
• Bottom-up
• Signal transduction model creation
• EPN context
• Map annotation
• Map drawing

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Outline

• EPE introduction
• Practical EPE installation
• EPE lookfeel
• EPE basic features
• Practical working with EPE

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Basic features

• Eclipse-based open plug-in design
• Metadata-oriented design
• Small number of basic objects to represent main
  concepts of the biological network
• Flexible visual presentation
• Internal RDBMS storage
• XML-based internal presentation
• Flexible export facility

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Eclipse open architecture

• Extension of basic features
• New DBMS
• New image format
• Implementation of domain specific features
• Model validation rules
• Export
• Visualisation of new type of data (simulaton
  results, experimental data)

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Implemented notations

• EMP/WIT metabolic pathway
• KEGG-like metabolic pathway description
• STKE
• Kitano process notation
• Kitano state notation
• Edinburgh process notation
• Biocarta-like artistic notation

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EMP/WIT outline
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EMP/WIT map
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KEGG-like notation
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STKE notation
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Biocarta like noation
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Edinburgh process notation
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Medium to large model creation

• EPE was used to create
• Reconstruction of the whole cell E. coli
  metabolism
• Reconstruction of whole human metabolism
• Reconstruction of the whole cell Synechocystis
  metabolism
• Reconstruction of Interferon pathway
• All KEGG diagrams were redrawn in EPE

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Outline

• EPE introduction
• Practical EPE installation
• EPE lookfeel
• EPE basic features
• Practical working with EPE

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Outline

• EPE introduction
• Practical EPE installation
• EPE lookfeel
• Practical working with EPE
• EPE basic features
• Practical drawing map in EPE

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Eclipse workbench
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Eclipse workbench
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Eclipse workbench
Zoom
Layouting buttons
Undo/Redo
Search
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Preferences

• Menu Window/Preferences

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Save as..

• Map could be saved as number of graphical formats
  (PNG, JPG, BMP, GIF)
• Map could be exported in internal XML
  representation (PWZ - PathWay Zipped)
• Map Could be imported from internal XML
  representation (PWZ - PathWay Zipped)

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Outline

• EPE introduction
• Practical EPE installation
• EPE lookfeel
• EPE basic features
• Practical working with EPE

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Search facility

• Search elements by text
• Do not sensitive to case
• Do not use exact match
• Search exact substring

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Advanced Pathway Search

• Allows to restrict search by
• Context
• Object
• Property
• Folder
• Could be case sensitive

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Search neighbourhood

• Search linked elements on the diagram
• Right click on empty part of the map
• Choose Select map/item by property

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Hyperlinks

• Link the map object with Internet or another map

• Useful for
• Hierarchical organisation of information
• Submodels
• References to external resources

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Hover text

• Shows text when mouse move over the object

• Useful for
• Short human readable description of object
• Summarized view of object properties

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Help text

• Open new pop-up by pressing F2 button
• Useful for
• Extended description of object with hyperlinks
  etc.

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Metadata based approach

• Every map links to Context
• Context store list of object tipes, which could
  be added to the map
• Each object type specify properties and default
  values for new object
• Context define way to import and export elements
  of the map

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Notations and drawing

• Elements of the context are on the Palette
• Once selected this element remains active unless
  you select another
• There is select selection tool.
• There is Marquee for area selection

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Outline

• EPE introduction
• Practical EPE installation
• EPE lookfeel
• EPE basic features
• Practical working with EPE

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Practical

• Create new map of Integrin context
• Draw some map
• Add Hover text to the elements
• Add Help text to the elements
• Save it as BMP image
• Save it as HTML page
• Export it to XML

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Practical

• Open EMP/Fatty Acid Metabolism Overview map
• Add link to FAS map from appropriate box

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(No Transcript)
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Context

• Description of metadata related to the map
• User-defined object types
• Domain-specific object properties
• Default values

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Base objects

• Shape
• Port
• Process
• Link
• Label

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Shape

• Shape represents the biological object or
  subsystem, treated as "a black box" .

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Port

• The port is the interface between the objects.
  The port is used to designate the part of the
  object, by which it could interact with other
  objects.

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Process

• Process visualizes sequence of events, e.g. a
  biochemical reaction or protein interaction.
• Chemical reactions,
• protein binding
• gene activation

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Link

• Link is used to represent any pair-wise relation
  between objects including "identity" or "act on"
  relations.

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Label

• Label is a visual object to represent textual
  information and to allow incorporate links to
  other maps and external resources.

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Types of properties

• Simple data
• Text
• Collections
• Visual data

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Simple data

• Simple string of ASCII characters
• EC 6.4.1.2
• PubMed 7567999

• Useful for
• Internal ID
• ID in external database (PubMed, GenBank etc.)
• Abbrevitions
• Simple descriptions
• Numerical values (constants, parameters etc.)

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Text

• Rich text with formatting, greek letters, fonts,
  colours, hyperlinks etc.

• Useful for
• Name of compounds, proteins etc.
• Human readable descriptions
• References to Internet resources
• References to the other maps

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Collections (Text Simple data)

• List of data of the same type

• Useful for
• List of references (to PubMed)
• List of synonyms or aliases

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Hyperlinks

• Link the map object with Internet or another map

• Useful for
• Hierarchical organisation of information
• Submodels
• References to external resources

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Hover text

• Shows text when mouse move over the object

• Useful for
• Short human readable description of object
• Summarized view of object properties

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Help text

• Open new pop-up by pressing F2 button
• Useful for
• Extended description of object with hyperlinks
  etc.

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Reference to value of the property

• There is simple language to reference values of
  properties of this object or related objects

• Useful for
• Default values of Help and Hover text
• Default value of the Label

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Visual properties colour
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Visual properties image
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Outline

• EPE introduction
• Practical EPE installation
• EPE lookfeel
• Practical working with EPE
• EPE basic features
• Practical drawing map in EPE

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Medium to large model creation

• EPE was used to create
• Reconstruction of the whole cell E. coli
  metabolism
• Reconstruction of whole human metabolism
• Reconstruction of the whole cell Synechocystis
  metabolism
• Reconstruction of Interferon pathway
• All KEGG diagrams

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Medium to large model creation

• Highly connected graph
• Huge amount of information
• Extremely difficult layout
• Difficult to read and navigate
• Extremely difficult to maintain

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Top-down Bottom-up

• Top-down
• Based upon genome information
• Focused on protein function
• Generic
• Wide and shallow
• Bottom-up
• Based upon experiment and literature
• Focused on metabolites
• Very specific
• Deep and narrow

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Hierarchical organisation of information

• Information is organised in tree-like structure
  with hyperlinks between maps
• Easy to navigate
• Easy to maintain
• Easy to develop
• Top-down and bottom up technology are supported
  naturally

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High level outline
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Low level details
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Middle level KEGG approach