Improving the Management of Computational Models:
storage – retrieval & ranking – version control
More information and slides to download at http://sems.uni-rostock.de/2013/12/martin-visits-the-ebi/
Axa Assurance Maroc - Insurer Innovation Award 2024
Improving the Management of Computational Models -- Invited talk at the EBI
1. SYSTEMS BIOLOGY
BIOINFORMATICS
ROSTOCK
SE S
simulation experiment management system
Improving the Management of
Computational Models
storage – retrieval & ranking – version control
M AR TIN S CHARM1,2 , R ON H ENKEL1 , DAGMAR WALTEMATH1 ,
O LAF W OLKENHAUER1,3
1
2
3
Department of Systems Biology & Bioinformatics, University of Rostock
Department of Computer Science, University of Oxford
Stellenbosch Institute for Advanced Study, South Africa
http:/
/sems.uni-rostock.de
European Bioinformatics Institute
UK 2013
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
1
2. 31
462 + 501 + x · 103
216 + 196
#models
Introduction
2013-06-18
•
•
•
Number of models is steadily increasing
Models tend to get more complex
Continuous development
2009-06-16
2005-04-11
time
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
2
4. Introduction
#Versions
•
•
•
Number of models is steadily increasing
Models tend to get more complex
Continuous development
time
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
2
10. SE S
SYSTEMS BIOLOGY
BIOINFORMATICS
ROSTOCK
simulation experiment management system
Retrieval
is
CP
isVersion
Pubm
ed:
183127
0
envi
ron
men
t
Model
refere
nce
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ation
CP
T
ask
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t
store
Datag
enera
tor
V
aria
ble
Inte
rpro
:
IPR
006
670
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0056
23
CP
time
time
time
CP
V
aria
ble
C2
Do
cu
me
T
ys
nt
on
19
91
Cel
l
Cy
cle
6
var
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CP
19
91
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l
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cle
6
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med:
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edBy
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l
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ron
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edBy
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ion
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16
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act
ion
3
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isDescribedBy
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l
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ot:P0
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n_19
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nt
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med:
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1831
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111
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hasPart
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ment
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edBy
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act
ion
3
19
91
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l
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cle
6
var
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edBy
CP
isVersion
Of
Do
cu
me
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ys
nt
on
19
91
Cel
l
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cle
6
var
C2
isVersion
Of
Do
cu
me
T
ys
nt
on
Re
act
ion
3
Pubm
ed:
183127
0
CP
is
Graph Database
C2
GO:0
0056
23
CP
time
time
time
CP
C2
rank
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cu
me
T
ys
nt
on
T
ask
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t
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4551
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me
T
ys
nt
on
19
91
Cel
l
Cy
cle
6
var
Docu
ment
Model
refere
nce
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L
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act
ion
3
T
ask
Inte
rpro
:
IPR
006
670
GO:0
0056
23
Outpu
t
isVersion
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ot:P0
4551
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med:
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1831
Path
270
way
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111
isDescrib
edBy
is
Cel
l
pM
Datag
enera
tor
is
isVersion
Of
T
ask
hasPart
isVersion
Of
ECCode:
3.1.3.
16
Simul
ation
Simul
ation
CP
Cel
l
pM
Outpu
t
Docu
ment
SEDM
L
Model
refere
nce
C2
is
is
ECCode:
3.1.3.
16
Datag
enera
tor
Pub
med:
Kegg
1831
Path
270
way
sce04
111
isDescrib
edBy
CP
isVersion
Δ
Simul
ation
C2
isVersion
Of
track development
SEDM
L
Model
refere
nce
19
91
Cel
l
Cy
cle
6
var
Re
act
ion
3
hasPart
Δ
Docu
ment
isVersion
Of
Version 2
Inte
rpro
:
IPR
006
670
GO:0
0056
23
Doc
ume
nt
V
aria
ble
latest
V
aria
ble
T
yso
n_19
91
C2
Version Control
CP
isDescribedBy
envi
ron
men
t
C2
Version 1
time
time
Pubm
ed:
183127
0
CP
time
CP
C2
Ranking
http:/
/sems.uni-rostock.de/
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
5
12. Storage
Available Data
Model & Simulation
•
•
Dec 4, 2013
Constituent names
XML encoded
representation
Annotation & Ontologies
•
•
Biochemical
background
Synonyms
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
A model’s network
•
•
•
Model structure
Aggregation values
Model related data
7
13. Storage
GraphDB
Tyson 1991 - SBML
Document
Model
Tyson1991
Cell Cycle 6
var
isDescribedBy
Entities
Reaction3
C2
is
CP
Pubmed:
1831270
Kegg Pathway
sce04111
pM
Cell
asProduct
Annotations
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
Interpro:
IPR006670
is
hasPart
isContainedIn
isVersion
isVersionOf
isVersionOf
asReactant
GO:0005623
fig. courtesy R. Henkel
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
8
14. Storage
GraphDB
Tyson 1991 - CellML
Document
Model
Model
Component
Variable
sodium
channel
m
v
is_connected
time
envmt
has_annotation
is_connected
time
time
Pubmed:
12991237
sodium
channel m
gate
v
m
is_mapped_to
fig. courtesy R. Henkel
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
9
15. Storage
GraphDB
Tyson 1991 - SED-ML
Document
Simulation
Entity
SEDML
Modelrefere
nce
Simulation
Task
Output
Datagenera
tor
Variable
Variable
Variable
fig. courtesy R. Henkel
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
10
18. Storage
GraphDB
Models
Model related data
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
EC-Code:
3.1.3.16
Dec 4, 2013
Uniprot:P04551
Uniprot:P04551
Interpro:
IPR006670
is
hasPart
isContainedIn
isVersion
isVersionOf
isVersionOf
asReactant
GO:0005623
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
19. Storage
GraphDB
Models
Model related data
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersion
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isContainedIn
Interpro:
IPR006670
GO:0005623
Document
Model
sodium
channel
m
v
is_connected
time
envmt
time
has_annotation
is_connected
time
Pubmed:
12991237
sodium
channel m
gate
v
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
20. Storage
GraphDB
Models
Model related data
Document
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
Modelrefere
nce
Simulation
Task
Output
Datagenera
tor
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
GO:0005623
Variable
Document
Model
sodium
channel
m
v
is_connected
time
envmt
time
has_annotation
is_connected
time
Pubmed:
12991237
sodium
channel m
gate
v
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
21. Storage
GraphDB
Models
Model related data
Document
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
Modelrefere
nce
Simulation
Task
Datagenera
tor
Output
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
Variable
GO:0005623
Document
Model
has_annotation
SBO:
Ontology
Pubmed:
12991237
SBO:0000
sodium
channel
is_connected
envmt
is_connected
sodium
channel m
gate
isA
SBO:064
m
v
time
time
time
v
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
22. Storage
GraphDB
Models
Model related data
Document
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
Modelrefere
nce
Simulation
Task
Datagenera
tor
Output
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
Variable
GO:0005623
Document
Model
has_annotation
SBO:
Ontology
Pubmed:
12991237
SBO:0000
sodium
channel
is_connected
envmt
is_connected
sodium
channel m
gate
isA
SBO:064
m
v
time
time
time
v
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
23. Storage
GraphDB
Models
Model related data
Document
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Modelrefere
nce
Cell
Simulation
Task
Datagenera
tor
Output
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
Variable
GO:0005623
Document
Model
has_annotation
SBO:
Ontology
Pubmed:
12991237
SBO:0000
sodium
channel
is_connected
envmt
is_connected
sodium
channel m
gate
isA
SBO:064
m
v
time
time
time
v
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
m
is_mapped_to
Henkel et al. 2013, Graph-based storage of computational biology models and associated simulations, in preparation
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
24. Storage
GraphDB
Models
Index
Model related data
Document
Document
Model
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersion
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isContainedIn
Interpro:
IPR006670
GO:0005623
Document
Model
has_annotation
Id
Name
Component
Variable
Species
Reaction
Compartment
Modelrefere
nce
Simulation
Task
Datagenera
tor
Output
Variable
Variable
SBO:
Ontology
Pubmed:
12991237
SBO:0000
sodium
channel
is_connected
envmt
is_connected
sodium
channel m
gate
isA
SBO:064
m
v
time
time
time
v
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
25. Storage
GraphDB
Models
Index
Model related data
Document
Document
Model
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
Publication
Modelrefere
nce
Simulation
Task
Datagenera
tor
Output
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
GO:0005623
Document
Model
has_annotation
Title
Journal
Abstract
Authors
Variable
SBO:
Ontology
Pubmed:
12991237
SBO:0000
sodium
channel
is_connected
envmt
is_connected
sodium
channel m
gate
isA
SBO:064
m
v
time
time
time
v
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
26. Storage
GraphDB
Models
Index
Model related data
Document
Document
Model
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
Publication
Modelrefere
nce
Simulation
Task
Datagenera
tor
Output
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
Person
Variable
GO:0005623
Document
Model
sodium
channel
is_connected
envmt
has_annotation
is_connected
First name
Last name
Organization
Email
Pubmed:
12991237
sodium
channel m
gate
SBO:
Ontology
SBO:0000
isA
SBO:064
m
v
time
time
time
v
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
27. Storage
GraphDB
Models
Index
Model related data
Document
Document
Model
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
Publication
Modelrefere
nce
Simulation
Task
Datagenera
tor
Output
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
Person
Variable
GO:0005623
Document
Annotation
Model
has_annotation
SBO:
Ontology
Pubmed:
12991237
SBO:0000
sodium
channel
is_connected
envmt
is_connected
sodium
channel m
gate
URI
Description
isA
SBO:064
m
v
time
time
time
v
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
m
is_mapped_to
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
28. Storage
GraphDB
Models
Index
Model related data
Document
Document
Model
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
SEDML
Kegg Pathway
sce04111
is
pM
Cell
Publication
Modelrefere
nce
Simulation
Task
Datagenera
tor
Output
asProduct
asReactant
isContainedIn
EC-Code:
3.1.3.16
Uniprot:P04551
Uniprot:P04551
is
hasPart
isVersionOf
isVersionOf
isVersion
Variable
Interpro:
IPR006670
Person
Variable
GO:0005623
Document
Annotation
Model
sodium
channel
is_connected
envmt
has_annotation
is_connected
SBO:
Ontology
Pubmed:
12991237
SBO:0000
Simulation
sodium
channel m
gate
isA
SBO:064
m
v
time
time
is_mapped_to
Dec 4, 2013
time
v
m
SBO:544
SBO:004
SBO:231
SBO:003
SBO:236
SBO:545
Id
Name
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
12
29. retrieval & ranking
Example
Show me models by
Tyson describing the cell
cycle and have cdc2!
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
isContainedIn
is
hasPart
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isVersion
Person
Annotation
Uniprot:P04551
Dec 4, 2013
Uniprot:P04551
Interpro:
IPR006670
GO:0005623
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
13
30. retrieval & ranking
Example
Show me models by
Tyson describing the cell
cycle and have cdc2!
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
isContainedIn
is
hasPart
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isVersion
Person
Annotation
Uniprot:P04551
Dec 4, 2013
Uniprot:P04551
Interpro:
IPR006670
GO:0005623
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
13
31. retrieval & ranking
Example
Show me models by
Tyson describing the cell
cycle and have cdc2!
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
isContainedIn
is
hasPart
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isVersion
Person
Annotation
Uniprot:P04551
Dec 4, 2013
Uniprot:P04551
Interpro:
IPR006670
GO:0005623
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
13
32. retrieval & ranking
Example
Show me models by
Tyson describing the cell
cycle and have cdc2!
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
isContainedIn
is
hasPart
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isVersion
Person
Annotation
Uniprot:P04551
Dec 4, 2013
Uniprot:P04551
Interpro:
IPR006670
GO:0005623
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
13
33. retrieval & ranking
Example
Show me models by
Tyson describing the cell
cycle and have cdc2!
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
isContainedIn
is
hasPart
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isVersion
Person
Annotation
Uniprot:P04551
Dec 4, 2013
Uniprot:P04551
Interpro:
IPR006670
GO:0005623
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
13
34. retrieval & ranking
Example
Show me models by
Tyson describing the cell
cycle and have cdc2!
Document
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
isContainedIn
is
hasPart
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isVersion
Person
Annotation
Uniprot:P04551
Dec 4, 2013
Uniprot:P04551
Interpro:
IPR006670
GO:0005623
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
13
35. retrieval & ranking
Example
Document
Thank you!
isDescribedBy
Tyson1991
Cell Cycle 6
var
Reaction3
C2
CP
Pubmed:
1831270
Kegg Pathway
sce04111
is
pM
Cell
asProduct
asReactant
Person
is
hasPart
isVersion
1. (0.859) Tyson1991 - Cell Cycle 6 var
2. (0.854) Tyson2001_Cell_Cycle_Regulation
3. (0.477) Chen2004 - Cell Cycle Regulation
isVersionOf
isVersionOf
EC-Code:
3.1.3.16
isContainedIn
Annotation
Uniprot:P04551
Uniprot:P04551
Interpro:
IPR006670
GO:0005623
Henkel et al. 2010: Ranked retrieval of Computational Biology models
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
13
36. Version Control
track versions
version x-1
version x
version x+1
what happened ?
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
14
37. Version Control
track versions
version x-1
version x
version x+1
what happened ?
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
14
38. Model Evolution
Example: Cell Cycle
Modeling the cell division...
Cyclin
Cdc2
P
Cyclin
Cdc2
P
John J Tyson, 1991
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
15
39. Model Evolution
Example: Cell Cycle
Modeling the cell division...
Cyclin
Cdc2
P
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte
Cyclin
Cyclin
Cdc2
Cdc2
P
P
John J Tyson, 1991
Cdc25∗
Wee1
Cdc25
Wee1∗
Cyclin
Cdc2
P
Bela Novak and John J Tyson, 1993
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
15
40. Model Evolution
Example: Cell Cycle
Modeling the cell division...
Quantitative analysis of a molecular model of mitotic control in Fission yeast
Cyclin
Cdc2
Cyclin
P
Cdc2
P
Mik1
Cdc25
∗
Wee1
Cyclin
Cdc2
Cdc2
P
John J Tyson, 1991
Cdc25∗
Wee1∗
Cdc25
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte
Cyclin
Mik1∗
Cyclin
P
Cdc2
P
Bela Novak and John J Tyson, 1995
Wee1
Cdc25
Wee1∗
Cyclin
Cdc2
P
Bela Novak and John J Tyson, 1993
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
15
41. Model Evolution
Example: Cell Cycle
Modeling the cell division...
Quantitative analysis of a molecular model of mitotic control in Fission yeast
Cyclin
Cdc2
Cyclin
Modeling the control of DNA replication in fission yeast
P
Cdc2
P
Mik1∗
Cyclin
Mik1
Cdc25
∗
Cdc2
Cdc25
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte
Cyclin
Cdc2
Cdc25∗
Cyclin
Cdc2
P
John J Tyson, 1991
Cdc25∗
Wee1
Cdc2
Mik1∗
Wee1∗
Cyclin
Cdc2
Wee1∗
Cyclin
Cdc2
Wee1
Wee1∗
P
Bela Novak and John J Tyson, 1995
Wee1
Mik1
Cdc25
Cyclin
P
Cdc25
P
P
Cyclin
P
Cdc2
P
Rum1
Bela Novak and John J Tyson, 1993
Bela Novak and John J Tyson, 1997
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
15
42. Version Control
good news
A
RB/E2F
free E2F
RB/E2F
r
A
C
RB-Phos
r
E
s
C
B
cycE/cdk2
D
new insights
RB-Hypo
D
cycE/cdk2
free E2F
B
RB-Hypo
Waltemath et al.: Improving the reuse of computational models through version
control. Bioinformatics (2013) 29(6): 742-728;
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
16
44. BiVeS
Difference Detection
free E2F
RB/E2F
r
A
C
RB/E2F
Biochemical Model Version Control System
RB-Phos
r
A
E
•
s
compares models encoded in standadized
and
)
formats (currently:
•
•
•
maps hierarchically structured content
C
B
cycE/cdk2
D
D
RB-Hypo
free E2F
cycE/cdk2
RB-Hypo
mapping
A
B
constructs a diff (in XML format)
is able to interprete this diff
A
D
<XML>
D
r
r
diff construction
C
C
E
B
s
B
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
Diff
moves
product of r: C
deletes
product of r: B
inserts
species: E
product of r: E
reaction s
</XML>
18
45. BudHat
Diff Visualization
r
A
RB/E2F
free E2F
RB/E2F
A
C
RB-Phos
r
E
s
C
B
cycE/cdk2
D
D
RB-Hypo
A
free E2F
B
cycE/cdk2
D
r
r
C
C
calls BiVeS to construct the diff
displays the result in various formats
• the XML diff
• a reaction network highlighting the
changes using
• a human readable report
A
D
RB-Hypo
•
•
E
B
s
E
B
s
<XML>
Diff
moves
product of r: C
deletes
product of r: B
inserts
species: E
product of r: E
reaction s
A
</XML>
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
r
B
C
D
19
46. Applications
Communicating Changes
Novak & Tyson ’93: Numerical analysis of a comprehensive model of M-phase control in Xenopus
oocyte extracts and intact embryos
Biomodels Database BIOMD0000000107:
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
20
47. Applications
Communicating Changes
Fixed the model → How to communicate the changes?
Unix diff?
1c1
< <?xml version=’1.0’ encoding=’UTF-8’ standalone=’no’?>
--> <?xml version="1.0" encoding="UTF-8" standalone="no"?>
287 lines...
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
21
48. Applications
Communicating Changes
Fixed the model → How to communicate the changes?
BiVeS Diff?
<?xml version="1.0" encoding="UTF-8" standalone="no"?>
<bives type="fullDiff">
<update/>
<delete>
<node id="1" oldChildNo="1" oldParent="/listOfReactions[1]/reaction[
<attribute id="2" name="rdf:resource" oldPath="/listOfReactions[1]/r
<node id="5" oldChildNo="4" oldParent="/listOfReactions[1]/reaction[
<node id="6" oldChildNo="1" oldParent="/listOfReactions[1]/reaction[
<attribute id="7" name="species" oldPath="/listOfReactions[1]/reacti
</delete>
<insert>
<attribute id="3" name="metaid" newPath="/listOfReactions[1]/reactio
<attribute id="4" name="metaid" newPath="/listOfReactions[1]/reactio
<attribute id="9" name="metaid" newPath="/listOfReactions[1]/reactio
<node id="10" newChildNo="1" newParent="/listOfReactions[1]/reaction
much smarter, but still 24 lines..
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
21
49. Applications
Communicating Changes
Fixed the model → How to communicate the changes?
BiVeS Diff: Highlighted chemical reaction network
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
21
50. Applications
Communicating Changes
Fixed the model → How to communicate the changes?
BiVeS Diff: Report
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
21
57. Summary
•
SEMS develops methods for improved model management
• Storage
• Retrieval & Ranking
• Version Control
•
... and implements these methods in tools that are
• modularly designed
• open source
• easy to integrate
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
26
58. Future
•
Support for further standards
• PharmML
• CombineArchive
• SBGN
• respect further ontologies in storage/search
•
Improved version control
• mapping w/ respect to biological meaning
• scoring schemes for differences
• filter for changes
•
Improved availability and analyzability of data
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
27
59. SYSTEMS BIOLOGY
BIOINFORMATICS
ROSTOCK
SE S
simulation experiment management system
Thank you for your attention!
SEMS group
Dagmar Waltemath
Ron Henkel
Martin Peters
Markus Wolfien
Rebekka Alm
Olaf Wolkenhauer
@SemsProject
http://sems.uni-rostock.de
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
28
62. BiVeS
Integration
jvm
network
cmd
java -jar BiVeS.jar path/to/versionA path/to/versionB
git diff 88fea1cddf b64477d742 model.file
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
29
63. BiVeS -vs- Unix’ Diff
Artifacts
delete a single line in an XML:
<variable name="T" units="kelvin" initial_value="295" public_interface="out"/>
for Unix’ diff it is 1 operation. Bives detects 5 operations (delete node variable
and 4 attributes).
Worse if multiple nodes on the same line:
<para><emphasis><ulink url="caffeine.zip">Caffeine</ulink></emphasis> - Caffeine-induced Ca2+ transients from 18 i
And worst if whole document only 1 line → max. 2 operations for the Unix diff tool.
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
30
64. CombineArchive
Single file containing models and model related data:
•
•
simulation experiment descriptions in SED-ML
graphical representations in SBGN-ML
necessary for the description of a model and all associated data and procedures
→ simplifies exchange
Proposal by Nicolas Le Novère, Frank Bergmann, and Richard Adams
http://co.mbine.org/documents/archive
We developed a JAVA library to create/read/manipulate CombineArchives
http://sems.uni-rostock.de/projects/combinearchive/
→ database import/export, difference detection between whole archives
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
31
65. BiVeS
Mapping
•
•
•
•
input: 2 XML documents
map unambiguos
nodes/subtrees
propagate mapping up/down
exploit further knowledge of
biological systems
same ID
...
...
same
subtree
hash
... ... ...
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
... ... ...
32
66. BiVeS
Mapping
•
•
•
•
input: 2 XML documents
map unambiguos
nodes/subtrees
propagate mapping up/down
exploit further knowledge of
biological systems
...
eq. netw.
... ... ...
Dec 4, 2013
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
...
... ... ...
32
67. BiVeS
Mapping
A
•
•
•
•
input: 2 XML documents
map unambiguos
nodes/subtrees
propagate mapping up/down
exploit further knowledge of
biological systems
B
A
C
D
C
E
D
A
SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer
E
B
C
D
Dec 4, 2013
B
E
32