most: exploring differences between versions of models in biomodels and in the physiome model...
TRANSCRIPT
European Bioinformatics Institute, Cambridge, UK - The 12th of January 2017
MOST: exploring differences between versions of models in BioModels and in the Physiome Model Repository
Tom Gebhardt, Martin Scharm, Vasundra Touré, Dagmar Waltemath, Olaf WolkenhauerDepartment of Systems Biology and Bioinformatics, University of Rostock
http://sems.uni-rostock.de/
2
Who I am
Project SBGN-ED+ ● Improvement of software (SBGN-ED) & library (libSBGN)● Outreach events (SBGN workshop @COMBINE 2016)● Symbol of the month
STON Master thesisStorage and management of Systems Biology models in graph databases.
2011-2013 BSc Living Sciences
2013-2015 MSc Bioinformatics and Biostatistics
Since Sep 2015 Scientific staff member
doi: 10.1186/s12859-016-1394-x
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Current SEMS projects
Integrated storage & retrieval system (MASYMOS)
doi: 10.1093/database/bau130
Search across heterogeneous data, ontologies, and structures
BioModelsPhysiome Model repository
Tailor-made storage systems (STON, SED-ML DB)
Using graph databases to integrate standardised model-based data
SED-ML DB in JWS Online
Tailor-made storage systems (STON, SED-ML DB)
doi: 10.1186/s12859-016-1394-x
4
Current SEMS projects
doi: 10.1186/s13326-016-0080-2
Physiome Model repository
Model version control (BiVeS & COMODI)
Changes of a model over time
doi: 10.1093/bioinformatics/btv484
Managing COMBINE archives (CombineArchiveWeb)
Explore, edit, share, publish archives
doi: 10.7287/peerj.preprints.639v1
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Current SEMS projects
doi: 10.1186/s13326-016-0080-2
Physiome Model repository
Changes of a model over time
doi: 10.1093/bioinformatics/btv484
Managing COMBINE archives (CombineArchiveWeb)
Explore, edit, share, publish archives
doi: 10.7287/peerj.preprints.639v1
Model version control (BiVeS & COMODI)
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Motivation: number of models increases
BioModels (BM)
Physiome Model Repository (PMR)
Scharm et al (2017), in preparation.
#models(BM & PMR)
3575
#Mod
els
in th
e R
epos
itory
Apr 0
5
Jun
06
Jul 0
7
Sep
08
Nov
09
Jan
11
Mar
12
Apr 1
3
Jun
14
Aug
15
Oct
16
0
500
1000
1500
2000
Apr 0
5
Jun
06
Jul 0
7
Sep
08
Nov
09
Jan
11
Mar
12
Apr 1
3
Jun
14
Aug
15
Oct
16
0
5000
10000
15000
20000
25000
Avg
#Nod
es p
er M
odel
BioModelsPhysiome
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Motivation: models are changing
Biological models are constantly evolving, implying that several versions of a model can exist.
Figure: Scharm et al. (2015) - Oxford BIOINFORMATICS
How can we be informed of changes for a model of interest?
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MOST web interface
MOST provides an interactive visualisation of model changes in BM and in the PMR.
http://most.sems.uni-rostock.de
Tom Gebhardt
Example of BIOMD0000000005Tyson1991 - Cell Cycle 6 var
16 versions
version 2008-12-03version 2009-03-25
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MOST uses BiVeS for difference detection
Biochemical Model Version Control System
https://sems.uni-rostock.de/projects/bives/
MOST integrates BiVeS to generate descriptions of a model’s changes.
Martin Scharm Figure: Scharm et al. (2015) - Oxford BIOINFORMATICS
deletion
insertion
move
update
4 types of elements are distinguished:
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MOST uses BiVeS for difference detection
The BiVeS XML-diff output file is available for further processing.
http://most.sems.uni-rostock.de/
<?xml version="1.0" encoding="UTF-8"?><bives type="fullDiff" id="bivesPatch"> <!--BiVeS compiled with: [BiVeS FrameWork v1.9.1] [BiVeS Core v1.7.2] [BiVeS SBML v1.7.4] [BiVeS CellML v1.6.5] --> <update> <text id="1" oldParent="/sbml[1]/model[1]/notes[1]/body[1]/p[3]" newParent="/sbml[1]/model[1]/notes[1]/body[1]/p[3]" oldChildNo="1" newChildNo="1" oldPath="/sbml[1]/model[1]/notes[1]/body[1]/p[3]/text()[1]" newPath="/sbml[1]/model[1]/notes[1]/body[1]/p[3]/text()[1]" oldText="This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2008 The BioModels Team." newText="This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team." /> <...> </update> <delete> <node id="39" triggeredBy="3" oldParent="/sbml[1]/model[1]/listOfUnitDefinitions[1]" oldChildNo="5" oldPath="/sbml[1]/model[1]/listOfUnitDefinitions[1]/unitDefinition[5]" oldTag="unitDefinition" /> <attribute name="id" id="40" triggeredBy="39" oldValue="plitrepmin" oldPath="/sbml[1]/model[1]/listOfUnitDefinitions[1]/unitDefinition[5]" /> <...> </delete> <insert> <attribute name="metaid" id="55" newValue="_840210" newPath="/sbml[1]/model[1]/listOfReactions[1]/reaction[1]/kineticLaw[1]/listOfParameters[1]/parameter[1]" /> <...> </insert> <move> <node id="51" oldParent="/sbml[1]/model[1]" newParent="/sbml[1]/model[1]" oldChildNo="4" newChildNo="3"
oldPath="/sbml[1]/model[1]/listOfCompartments[1]" newPath="/sbml[1]/model[1]/listOfCompartments[1]" /> <node id="52" oldParent="/sbml[1]/model[1]" newParent="/sbml[1]/model[1]" oldChildNo="5" newChildNo="4"
oldPath="/sbml[1]/model[1]/listOfSpecies[1]" newPath="/sbml[1]/model[1]/listOfSpecies[1]" /> <...> </move></bives>
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MOST uses BiVeS for difference detection
The report of differences helps for human consumption.
http://most.sems.uni-rostock.de/
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MOST uses COMODI to classify changes
COMODI characterises differences in versions of computational models.
Scharm et al (2016) - Journal of Biomedical Semanticshttp://most.sems.uni-rostock.de/
wasTriggeredBy
affects
appliesTo
ChangeDeletion
Update
PermutationOfEntities
Move
Insertion
XmlEntity
XmlNode
ModelId
EntityIdentifier
XmlAttribute
ModelName
EntityName
XmlText
Target
ModelAnnotation
CreationDate
DateModificationDate
TextualDescription
OntologyReference
PersonContributor
Creator
Attribution
ModelDefinition
MathematicalModelDefinition
ComponentDefinition
EventDefinition
FunctionDefinition
KineticsDefinition
RuleDefinition
UnitDefinition
NetworkDefinition
HierarchyDefinition
VariableConnectionDefinition PortDefinition
ReactionNetworkDefinition
ParticipantDefinition
ReversibilityDefinition
ReactionDefinition
ModelEncoding
IdentifierEncoding
MetaIdEncoding
ModelSetup
ParameterSetup
SpeciesSetup
VariableSetup
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MOST uses COMODI to classify changes
A coloured map of the COMODI ontology gives an overview of applied changes.
Scharm et al (2016) - Journal of Biomedical Semanticshttp://most.sems.uni-rostock.de/
wasTriggeredBy
affects
appliesTo
ChangeDeletion
Update
PermutationOfEntities
Move
Insertion
XmlEntity
XmlNode
ModelId
EntityIdentifier
XmlAttribute
ModelName
EntityName
XmlText
Target
ModelAnnotation
CreationDate
DateModificationDate
TextualDescription
OntologyReference
PersonContributor
Creator
Attribution
ModelDefinition
MathematicalModelDefinition
ComponentDefinition
EventDefinition
FunctionDefinition
KineticsDefinition
RuleDefinition
UnitDefinition
NetworkDefinition
HierarchyDefinition
VariableConnectionDefinition PortDefinition
ReactionNetworkDefinition
ParticipantDefinition
ReversibilityDefinition
ReactionDefinition
ModelEncoding
IdentifierEncoding
MetaIdEncoding
ModelSetup
ParameterSetup
SpeciesSetup
VariableSetup
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Example data
How often do model changes?#model versions
(BM & PMR)
15 242
Scharm et al (2017), in preparation http://most.sems.uni-rostock.de/
BIO
MD
0001
BIO
MD0
021
BIO
MD
0041
BIO
MD
0061
BIO
MD
0081
BIO
MD0
101
BIO
MD
0121
BIO
MD
0141
BIO
MD
0161
BIO
MD
0181
BIO
MD
0201
BIO
MD
0221
BIO
MD
0241
BIO
MD
0261
BIO
MD
0281
BIO
MD
0301
BIO
MD
0321
BIO
MD
0341
BIO
MD
0361
BIO
MD
0381
BIO
MD
0401
BIO
MD
0421
BIO
MD
0441
BIO
MD
0463
BIO
MD
0483
BIO
MD
0512
BIO
MD
0546
Apr 05Jul 05
Jan 06Jun 06Oct 06Jan 07Jun 07Sep 07Mar 08Aug 08Dec 08Mar 09Jun 09Sep 09Jan 10Apr 10Sep 10Apr 11Sep 11Feb 12May 12Aug 12Dec 12Jun 13Nov 13Apr 14Sep 14Apr 15
May 16
0
510
50100
5001000
5000
17425
Frequency of updates of curated models in BioModels.
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Example data
1
3
7
20
55
148
403
1097
2981
8103
22026
59874
162755C
han
ges
#deltas(BM & PMR)
11 200
What type of changes are frequently applied?
deletion
insertion
move
update
updates
deletes
inserts
moves
document nodes
attributes
text nodes
1 5 10 50 100 500 1000
updates
deletes
inserts
moves
document nodes
attributes
text nodes
BM
PMR
Figures courtesy: Martin Scharm & Tom Gebhardt http://most.sems.uni-rostock.de/
Quantifying types of changes observed between two model versions in BM and in the PMR.
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Time for a demo!
http://most.sems.uni-rostock.de/
http://most.sems.uni-rostock.de/#m:BIOMD0000000107.xml,d1:2004-12-31,d2:2016-12-31,v:d
17
MOST uses DiVil to visualise changes
DiVil generates an SBGN map that visualises and colorises differences between two model versions.
Work in progress
RAF
ERK
MEK MEK
2P
ERK
MEK
P
ERK
P
RAF
P
ERK
2P
ADPATP
ATP ADP
ATP
ATP ADP
ADP
Version 1
MEK
2P
RAF
P
ERK
P
RAS
active
ERKERK
2P
ERK
RAS
MEK
P
RAF
ADP
ADP
ATP ATP
ATP
ADPATP
ADP
Version 2
18
MOST uses DiVil to visualise changes
DiVil generates an SBGN map that visualises and colorises differences between two model versions.
Work in progress
MEK
2P
RAS
ERK
RAF
P
RAF
RAS
active
ERK
2P
ERK
MEK
P
ERK
P
MEK
ATP
ATP
ATP ADP
ADP ADP
ADP
ATPADP
ATP
RAF
ERK
MEK MEK
2P
ERK
MEK
P
ERK
P
RAF
P
ERK
2P
ADPATP
ATP ADP
ATP
ATP ADP
ADP
Version 1
MEK
2P
RAF
P
ERK
P
RAS
active
ERKERK
2P
ERK
RAS
MEK
P
RAF
ADP
ADP
ATP ATP
ATP
ADPATP
ADP
Version 2Transition version
19
MOST uses DiVil to visualise changes
The SBGN-compliant graph will visually compare the networks in MOST.
http://most.sems.uni-rostock.de/
Work in progress
Differences Visualisation
compartment
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Summary of tools used in MOST
ModelCrawler – Retrieves the models from BM and the PMR
https://github.com/FreakyBytes/ModelCrawler
BiVeS – Detects differences between two versions of a model
https://github.com/SemsProject/BiVeS
https://github.com/SemsProject/BiVeS-Core
DiVil – Visualises the differences in a SBGN format (prototype)
https://github.com/Gebbi8/DiVil
21
SEMS is ending in July 2017...
Contact us to adopt a SEMS!
If you are interested in any of our projects
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Overview of the SEMS team
Dagmar WaltemathGroup Leader
Martin ScharmBiVeSCOMODICombineArchive
Tom GebhardtMOSTDiVil
Mariam NassarMORRE
Martin PetersCombineArchiveSED-ML DBModelCrawler
Ron HenkelMaSyMoS
Vasundra TouréSTONSBGN-ED+MOST
