Post on 31-Mar-2015
Edinburgh Pathway Edinburgh Pathway EditorEditor
a flexible tool for biological model creationa flexible tool for biological model creation
Anatoly SorokinAnatoly Sorokin
Edinburgh Centre for System Edinburgh Centre for System biology biology
12/01/2006 A. Sorokin
System biology System biology modelling gapmodelling gap
““Biologist can be divided into two Biologist can be divided into two classes: experimentalists who classes: experimentalists who observed things that cannot be observed things that cannot be explained, and theoreticians who explained, and theoreticians who explain things that cannot be explain things that cannot be observed.”observed.”
Katzir-KatchalskyKatzir-Katchalsky
12/01/2006 A. Sorokin
KnowledgeIntegration &
Databases
Network Reconstruction Network Reconstruction and Modelingand Modeling
Experimental Quantitative Data
Experimental Data
Expert Knowledge Literature
Pathway DatabasesQuestions:
Modes of actionIntervention sites
Hypothesis testing
Modelling ResultsValidate hypotheses
Hypothesis generationFind modes of action, intervention
sites, bindings, targets, etc.
Interesting modellingobservations: ‘gems
ATP ATP
ATPndkndk
dCDP dUDP
dUTP
UMPUDPCDP
T4 nrdABT4 nrdC
T5dut
T4 tdthyA
dCTP
ATP
ADPADP
ATPndk ndk
NH 3
dcd
PPi
H 2O
pyrHcmk
ATP ATP
ADP
PBS2dTMPase
dCMPSP8 deaminase
T4 dCTPase
ppk ppk
ppk ppk
dUDPase
rpsA
Electronic Networks
ModellingSimulation
12/01/2006 A. Sorokin
KnowledgeIntegration &
Databases
Network Reconstruction Network Reconstruction and Modelingand Modeling
Experimental Quantitative Data
Experimental Data
Expert Knowledge
Literature
Pathway Databases
Questions:
Modes of actionIntervention sites
Hypothesis testing
Modelling ResultsValidate hypotheses
Hypothesis generationFind modes of action, intervention
sites, bindings, targets, etc.
Interesting modellingobservations: ‘gems
ATP ATP
ATPndkndk
dCDP dUDP
dUTP
UMPUDPCDP
T4 nrdABT4 nrdC
T5dut
T4 tdthyA
dCTP
ATP
ADPADP
ATPndk ndk
NH 3
dcd
PPi
H 2O
pyrHcmk
ATP ATP
ADP
PBS2dTMPase
dCMPSP8 deaminase
T4 dCTPase
ppk ppk
ppk ppk
dUDPase
rpsA
Electronic Networks
Simulation
Modelling
12/01/2006 A. Sorokin
Two types of modelTwo types of model
Biological modelBiological model Keep expert Keep expert
knowledgeknowledge Proved by Proved by
experimentexperiment Variable level of Variable level of
detailsdetails Variable level of Variable level of
certaintycertainty
Numerical modelNumerical model Based on biological Based on biological
modelmodel Contains detailed Contains detailed
description of the description of the processprocess
Ready for Ready for simulationsimulation
Contains arbitrary Contains arbitrary assumptionsassumptions
12/01/2006 A. Sorokin
Biological modelsBiological models
12/01/2006 A. Sorokin
Mathematical modelsMathematical models
PDN = (SN,TN,ST-Edge,TS-Edge) where PDN = (SN,TN,ST-Edge,TS-Edge) where SN = ( SN = ( snsn 1 1 , , snsn2 2 ..., ..., snsni i ), ),
TN=( TN=( tntn 1 1 , , tntn2 2 ,..., ,..., tntnj j ), ),
ST-Edge = SN ST-Edge = SN ××N, N,
TS-Edge = TN TS-Edge = TN ××SN, SN,
and and snsn i =(sn j , i =(sn j , snsnk ,..., k ,..., snsnn : n : cmcmi ). i ).
12/01/2006 A. Sorokin
12/01/2006 A. Sorokin
Link model types Link model types togethertogether
Experimentalist orientedExperimentalist oriented Support biological modelsSupport biological models Support “Round trip” development Support “Round trip” development
Biologicalmodel
Numerical model
Purification, reduction,assumptions, parameters
Observation, Questions,Predictions
12/01/2006 A. Sorokin
System biology System biology modelling gapmodelling gap
Models are distributed in large Models are distributed in large number of papersnumber of papers
Models are published in informal Models are published in informal stylestyle
Difficult to trace all detailsDifficult to trace all details
12/01/2006 A. Sorokin
Systems Biology Markup Language (SBML)
XML-based language to share model XML-based language to share model informationinformation
Model of biological processModel of biological process Simulation orientedSimulation oriented Expect detailed description of the Expect detailed description of the
processprocess No structure to store annotation No structure to store annotation
datadata
12/01/2006 A. Sorokin
System Biology Graphical System Biology Graphical notation (SBGN) notation (SBGN)
Standard Graphical notationStandard Graphical notation RequirementsRequirements
(1) Expressiveness: The notation system should be able to describe every possible relationship among genes and proteins, as well as biological processes.
(2) Semantically unambiguous: Notation should be unambiguous.
(3) Visually unambiguous: Each symbol should be clearly identified and cannot be mistaken with other symbols. This feature should be maintained with low-resolution displays, as well as black/white printings.
(4) Extension Capability: The notation system shall be flexible enough to add new symbols and relationship in a consistent manner. This may include the use of color-coding to enhance expressiveness and readability, but information shall not be lost even with black and white displays.
12/01/2006 A. Sorokin
RequirementsRequirements Validation of networks vs. controlled vocabularies Validation of networks vs. controlled vocabularies
of Small Molecules, Genes, Proteins, and of Small Molecules, Genes, Proteins, and transcripts to control confusion of multiple transcripts to control confusion of multiple names across research areas.names across research areas.
Networks should allow adding of Networks should allow adding of Literature objects (Medline etc…)Literature objects (Medline etc…) Kinetic information to reactionsKinetic information to reactions Export in wide variety of formatsExport in wide variety of formats Any desired data related to model creationAny desired data related to model creation
Build in links to, and load Build in links to, and load publicly available data sources…publicly available data sources…
12/01/2006 A. Sorokin
Edinburgh Pathway Edinburgh Pathway EditorEditor
12/01/2006 A. Sorokin
Basic featuresBasic features Small number of basic objects to represent Small number of basic objects to represent
main concepts of the biological networkmain concepts of the biological network Metadata-oriented designMetadata-oriented design Flexible visual presentationFlexible visual presentation Hierarchical data storageHierarchical data storage Customisable direct link to external Customisable direct link to external
databasesdatabases Eclipse-based open plug-in designEclipse-based open plug-in design XML-based internal presentationXML-based internal presentation Export to SBML Export to SBML
12/01/2006 A. Sorokin
Main objectsMain objects
ShapeShape PortPort ProcessProcess LinkLink LabelLabel
12/01/2006 A. Sorokin
ShapeShape
ShapeShape represents the biological represents the biological object or subsystem, treated as "a object or subsystem, treated as "a black box" .black box" .
12/01/2006 A. Sorokin
PortPort
The port is used to designate the The port is used to designate the state of the object, in which it could state of the object, in which it could interact with other objects. The port interact with other objects. The port is the interface between the objects.is the interface between the objects.
12/01/2006 A. Sorokin
ProcessProcess
ProcessProcess visualises sequence of visualises sequence of eventsevents,, e.g. a biochemical reaction e.g. a biochemical reaction or protein interaction. or protein interaction. Chemical reactions, Chemical reactions, protein binding protein binding gene activationgene activation
12/01/2006 A. Sorokin
LinkLink
LinkLink is used to represent any pair- is used to represent any pair-wise relation between objects wise relation between objects including "identity" or "act on" including "identity" or "act on" relations. relations.
12/01/2006 A. Sorokin
LabelLabel
LabelLabel is a visual object to represent is a visual object to represent textual information and to allow textual information and to allow incorporate incorporate links to other maps and links to other maps and resources. resources.
12/01/2006 A. Sorokin
ContextContext
Description of metadata related to Description of metadata related to the mapthe map User-defined object typesUser-defined object types Domain-specific object propertiesDomain-specific object properties Default valuesDefault values
12/01/2006 A. Sorokin
Types of properiesTypes of properies
Simple dataSimple data TextText CollectionsCollections Visual dataVisual data
12/01/2006 A. Sorokin
Simple dataSimple data
Simple string of Simple string of characters:characters:EC: 6.4.1.2EC: 6.4.1.2
PubMed: 7567999PubMed: 7567999
Useful forUseful for ID in external ID in external
database (PubMed, database (PubMed, GenBank etc.)GenBank etc.)
AbbrevitionsAbbrevitions Simple descriptionsSimple descriptions Numerical values Numerical values
(constants, (constants, parameters etc.)parameters etc.)
12/01/2006 A. Sorokin
TextText Rich text with Rich text with
formatting, greek formatting, greek letters, fonts, colours, letters, fonts, colours, hyperlinks etc.hyperlinks etc.
Useful for:Useful for: Name of Name of
compounds, compounds, proteins etc.proteins etc.
Human readable Human readable descriptionsdescriptions
References to References to Internet resourcesInternet resources
12/01/2006 A. Sorokin
Collections (Text & Collections (Text & Simple data)Simple data)
List of data of the List of data of the same typesame type
List of references List of references (to PubMed)(to PubMed)
List of synonyms List of synonyms or aliasesor aliases
12/01/2006 A. Sorokin
HyperlinksHyperlinks
Link the map Link the map object with object with Internet or another Internet or another mapmap
Hierarchical Hierarchical organisation of organisation of informationinformation
SubmodelsSubmodels References to References to
external resourcesexternal resources
12/01/2006 A. Sorokin
Hover textHover text
Shows text when Shows text when mouse move on the mouse move on the objectobject
Useful forUseful for Detailed human Detailed human
readable readable description of description of objectobject
Summarized view Summarized view of object propertiesof object properties
12/01/2006 A. Sorokin
Help textHelp text
Open new pop-Open new pop-up by pressing up by pressing F2 buttonF2 button
Useful for:Useful for: Extended Extended
description of description of object with object with hyperlinks etchyperlinks etc
12/01/2006 A. Sorokin
Reference to value of the Reference to value of the propertyproperty
There is simple There is simple language to language to reference values of reference values of properties of this properties of this object or related object or related objects objects
Useful for Useful for Default values of Default values of
Help and Hover Help and Hover texttext
Default value of the Default value of the LabelLabel
12/01/2006 A. Sorokin
Visual properties: colourVisual properties: colour
12/01/2006 A. Sorokin
Visual properties: imageVisual properties: image
12/01/2006 A. Sorokin
Inheritance, default Inheritance, default value value
12/01/2006 A. Sorokin
Visual representationVisual representation
12/01/2006 A. Sorokin
Visual representationVisual representation
12/01/2006 A. Sorokin
Visual representationVisual representation
12/01/2006 A. Sorokin
Visual representationVisual representation
12/01/2006 A. Sorokin
Visual representationVisual representation
12/01/2006 A. Sorokin
Development teamDevelopment team
Igor Goryanin, The University of Igor Goryanin, The University of Edinburgh Edinburgh
Kirill Paliy, EMP Project Inc.Kirill Paliy, EMP Project Inc. Alex Selkov, EMP Project Inc.Alex Selkov, EMP Project Inc. Oleg Demin, Moscow State Oleg Demin, Moscow State
UniversityUniversity
www.bioinformatics.ed.ac.uk/epe/www.bioinformatics.ed.ac.uk/epe/
12/01/2006 A. Sorokin
Network Reconstruction Network Reconstruction and Modelingand Modeling
Experimental Quantitative Data
Experimental Data
NetworkReconstruction
ModellingSimulation
Expert Knowledge
Questions:Hypothesis testingModes of actionIntervention sites
Interesting modellingobservations: ‘gems”
KnowledgeIntegration &
Databases
Modelling ResultsValidate hypotheses
Hypothesis generationFind modes of action, intervention
sites, bindings, targets, etc.
Literature
Electronic Networks
ATP ATP
ATPndkndk
dCDP dUDP
dUTP
UMPUDPCDP
T4 nrdABT4 nrdC
T5dut
T4 tdthyA
dCTP
ATP
ADPADP
ATPndk ndk
NH 3
dcd
PPi
H 2O
pyrHcmk
ATP ATP
ADP
PBS2dTMPase
dCMPSP8 deaminase
T4 dCTPase
ppk ppk
ppk ppk
dUDPase
rpsA
Planning experiments
Pathway Databases
12/01/2006 A. Sorokin
Network Reconstruction Network Reconstruction and Modelingand Modeling
Experimental Quantitative Data
Experimental Data
BiologicalModel
ModellingSimulation
Expert Knowledge
Questions:Hypothesis testingModes of actionIntervention sites
Interesting modellingobservations: ‘gems”
KnowledgeIntegration &
Databases
Modelling ResultsValidate hypotheses
Hypothesis generationFind modes of action, intervention
sites, bindings, targets, etc.
Literature
Electronic Networks
ATP ATP
ATPndkndk
dCDP dUDP
dUTP
UMPUDPCDP
T4 nrdABT4 nrdC
T5dut
T4 tdthyA
dCTP
ATP
ADPADP
ATPndk ndk
NH 3
dcd
PPi
H 2O
pyrHcmk
ATP ATP
ADP
PBS2dTMPase
dCMPSP8 deaminase
T4 dCTPase
ppk ppk
ppk ppk
dUDPase
rpsA
Planning experiments
Pathway Databases
Literature