Written by Martin Scharm (University of Rostock), Ron Henkel (University of Rostock), Dagmar Waltemath (University of Rostock), Olaf Wolkenhauer (University of Rostock, Stellenbosch University), and presented by Martin Scharm (University of Rostock) as part of the Reproducible and Citable Data and Models Workshop in Warnemünde, Germany. September 14th - 16th 2015.
1. SYSTEMS BIOLOGY
BIOINFORMATICS
ROSTOCK
S E Ssimulation experiment management system
Improving the Management of
Computational Models
storage – retrieval & ranking – version control
MARTIN SCHARM
1,2
, RON HENKEL
1
, DAGMAR WALTEMATH
1
,
OLAF WOLKENHAUER
1,3
1
Department of Systems Biology & Bioinformatics, University of Rostock
2
Department of Computer Science, University of Oxford
3
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
4. Introduction
time
#Versions
• Number of models is steadily increasing
• Models tend to get more complex
• Continuous development
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 2
5. Introduction
Tasks
• Storage & Availability
• Search & Retrieval
• Version Control
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 3
6. Introduction
Tasks
• Storage & Availability
• Search & Retrieval
• Version Control
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 3
7. Introduction
Tasks
• Storage & Availability
• Search & Retrieval
• Version Control
?
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 3
8. Introduction
Tasks
• Storage & Availability
• Search & Retrieval
• Version Control
version x-1 version x version x+1
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 3
10. SYSTEMS BIOLOGY
BIOINFORMATICS
ROSTOCK
S E Ssimulation experiment management system
track development
store retrieve
rank
Retrieval
Ranking
Δ
Δ
Version 1
Version 2
latest
Version Control
Do
cu
me
ntTys
on
19
91
Cel
l
Cy
cle
6
var
C2 pM
Cel
l
Re
act
ion
3
CP
Unipr
ot:P0
4551
Unipr
ot:P0
4551
GO:0
0056
23
Inte
rpro
:
IPR
006
670
isVersion
Of
isVersion
hasPart
is
Pub
med:
1831
270
Kegg
Path
way
sce04
111
isDescrib
edBy
is
EC-
Code:
3.1.3.
16
isVersion
Of
Docu
ment
SEDM
L
Model
refere
nce
Outpu
t
Datag
enera
tor
Simul
ation
Task
Varia
ble
Varia
ble
Doc
ume
nt
Tyso
n_19
91
C2 CP
time
envi
ron
men
t
isDescribedBy
Pubm
ed:
183127
0
time timeCPC2 CP C2
Do
cu
me
ntTys
on
19
91
Cel
l
Cy
cle
6
var
C2 pM
Cel
l
Re
act
ion
3
CP
Unipr
ot:P0
4551
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ot:P0
4551
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0056
23
Inte
rpro
:
IPR
006
670
isVersion
Of
isVersion
hasPart
is
Pub
med:
1831
270
Kegg
Path
way
sce04
111
isDescrib
edBy
is
EC-
Code:
3.1.3.
16
isVersion
Of
Do
cu
me
ntTys
on
19
91
Cel
l
Cy
cle
6
var
C2 pM
Cel
l
Re
act
ion
3
CP
Unipr
ot:P0
4551
Unipr
ot:P0
4551
GO:0
0056
23
Inte
rpro
:
IPR
006
670
isVersion
Of
isVersion
hasPart
is
Pub
med:
1831
270
Kegg
Path
way
sce04
111
isDescrib
edBy
is
EC-
Code:
3.1.3.
16
isVersion
Of
Do
cu
me
ntTys
on
19
91
Cel
l
Cy
cle
6
var
C2 pM
Cel
l
Re
act
ion
3
CP
Unipr
ot:P0
4551
Unipr
ot:P0
4551
GO:0
0056
23
Inte
rpro
:
IPR
006
670
isVersion
Of
isVersion
hasPart
is
Pub
med:
1831
270
Kegg
Path
way
sce04
111
isDescrib
edBy
is
EC-
Code:
3.1.3.
16
isVersion
Of
Doc
ume
nt
Tyso
n_19
91
C2 CP
time
envi
ron
men
t
isDescribedBy
Pubm
ed:
183127
0
time timeCPC2 CP C2
Do
cu
me
ntTys
on
19
91
Cel
l
Cy
cle
6
var
C2 pM
Cel
l
Re
act
ion
3
CP
Unipr
ot:P0
4551
Unipr
ot:P0
4551
GO:0
0056
23
Inte
rpro
:
IPR
006
670
isVersion
Of
isVersion
hasPart
is
Pub
med:
1831
270
Kegg
Path
way
sce04
111
isDescrib
edBy
is
EC-
Code:
3.1.3.
16
isVersion
Of
Do
cu
me
ntTys
on
19
91
Cel
l
Cy
cle
6
var
C2 pM
Cel
l
Re
act
ion
3
CP
Unipr
ot:P0
4551
Unipr
ot:P0
4551
GO:0
0056
23
Inte
rpro
:
IPR
006
670
isVersion
Of
isVersion
hasPart
is
Pub
med:
1831
270
Kegg
Path
way
sce04
111
isDescrib
edBy
is
EC-
Code:
3.1.3.
16
isVersion
Of
Doc
ume
nt
Tyso
n_19
91
C2 CP
time
envi
ron
men
t
isDescribedBy
Pubm
ed:
183127
0
time timeCPC2 CP C2
Graph Database
Docu
ment
SEDM
L
Model
refere
nce
Outpu
t
Simul
ation
Task
Docu
ment
SEDM
L
Model
refere
nce
Outpu
t
Datag
enera
tor
Simul
ation
Task
Varia
ble
Varia
ble
Docu
ment
SEDM
L
Model
refere
nce
Outpu
t
Datag
enera
tor
Simul
ation
Task
http://sems.uni-rostock.de/
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 5
12. Storage
Available Data
Model & Simulation Annotation & Ontologies A model’s network
• Constituent names
• XML encoded
representation
• Biochemical
background
• Synonyms
• Model structure
• Aggregation values
• Model related data
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 7
13. Storage
GraphDB
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Tyson 1991 - SBML
Model
Entities
Annotations
fig. courtesy R. Henkel
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 8
18. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
19. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
20. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
21. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
22. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
23. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
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 Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Index
Model
Id
Name
Component
Variable
Species
Reaction
Compartment
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
25. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Index
Model
Publication
Title
Journal
Abstract
Authors
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
26. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Index
Model
Publication
Person
First name
Last name
Organization
Email
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
27. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Index
Model
Publication
Person
Annotation
URI
Description
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
28. Storage
GraphDB
Models Model related data
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Document
Model
sodium
channel
sodium
channel m
gate
time
envmt
has_annotation Pubmed:
12991237
time timevm v m
is_connected is_connected
is_mapped_to
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation Task
Variable
Variable
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Index
Model
Publication
Person
Annotation
Simulation
Id
Name
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 12
29. retrieval & ranking
Example
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Show me models by
Tyson describing the cell
cycle and have cdc2!
Person
Annotation
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 13
30. retrieval & ranking
Example
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Show me models by
Tyson describing the cell
cycle and have cdc2!
Person
Annotation
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 13
31. retrieval & ranking
Example
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Show me models by
Tyson describing the cell
cycle and have cdc2!
Person
Annotation
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 13
32. retrieval & ranking
Example
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Show me models by
Tyson describing the cell
cycle and have cdc2!
Person
Annotation
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 13
33. retrieval & ranking
Example
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Show me models by
Tyson describing the cell
cycle and have cdc2!
Person
Annotation
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 13
34. retrieval & ranking
Example
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Show me models by
Tyson describing the cell
cycle and have cdc2!
Person
Annotation
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 13
35. retrieval & ranking
Example
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623
Interpro:
IPR006670
isVersionOf
isVersion
hasPart
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isVersionOf
Thank you!
Person
Annotation
1. (0.859) Tyson1991 - Cell Cycle 6 var
2. (0.854) Tyson2001_Cell_Cycle_Regulation
3. (0.477) Chen2004 - Cell Cycle Regulation
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
version x-1 version x version x+1
what happened ?
track versions
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 14
37. Version Control
version x-1 version x version x+1
track versions
what happened ?
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 14
38. Model Evolution
Example: Cell Cycle
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Modeling the cell division...
John J Tyson, 1991
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 15
39. Model Evolution
Example: Cell Cycle
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Cdc25Cdc25∗
Wee1 Wee1∗
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte
Bela Novak and John J Tyson, 1993
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Modeling the cell division...
John J Tyson, 1991
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 15
40. Model Evolution
Example: Cell Cycle
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Cdc25Cdc25∗
Wee1 Wee1∗
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte
Bela Novak and John J Tyson, 1993
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Cdc25Cdc25∗
Mik1 Mik1∗
Wee1 Wee1∗
Quantitative analysis of a molecular model of mitotic control in Fission yeast
Bela Novak and John J Tyson, 1995
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Modeling the cell division...
John J Tyson, 1991
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 15
41. Model Evolution
Example: Cell Cycle
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Cdc25Cdc25∗
Wee1 Wee1∗
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte
Bela Novak and John J Tyson, 1993
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Cdc25Cdc25∗
Mik1 Mik1∗
Wee1 Wee1∗
Quantitative analysis of a molecular model of mitotic control in Fission yeast
Bela Novak and John J Tyson, 1995
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Modeling the cell division...
John J Tyson, 1991
Cyclin
Cdc2 P
Cyclin
Cdc2 P
Cdc25Cdc25∗
Mik1 Mik1∗
Wee1 Wee1∗
Cyclin
Cdc2 P
Rum1
Modeling the control of DNA replication in fission yeast
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 r C
B
D
cycE/cdk2
RB/E2F
RB-Hypo
free E2F
A r
B
C
D
E s
RB/E2F
RB-Hypo
free E2F
cycE/cdk2
RB-Phos
new insights
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
43. BiVeS
Difference Detection
A r C
B
D
cycE/cdk2
RB/E2F
RB-Hypo
free E2F
A r
B
C
D
E s
RB/E2F
RB-Hypo
free E2F
cycE/cdk2
RB-Phos
A
r
B
C
D
A
r
B
C
D
E
s
Biochemical Model Version Control System
• compares models encoded in standadized
formats (currently: and )
• maps hierarchically structured content
mapping
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 17
44. BiVeS
Difference Detection
A r C
B
D
cycE/cdk2
RB/E2F
RB-Hypo
free E2F
A r
B
C
D
E s
RB/E2F
RB-Hypo
free E2F
cycE/cdk2
RB-Phos
A
r
B
C
D
A
r
B
C
D
E
s
Biochemical Model Version Control System
• compares models encoded in standadized
formats (currently: and )
• maps hierarchically structured content
• constructs a diff (in XML format)
• is able to interprete this diff
<XML>
Diff
moves
product of r: C
deletes
product of r: B
inserts
species: E
product of r: E
reaction s
</XML>
mapping
diff construction
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 18
45. BudHat
Diff Visualization
A r C
B
D
cycE/cdk2
RB/E2F
RB-Hypo
free E2F
A r
B
C
D
E s
RB/E2F
RB-Hypo
free E2F
cycE/cdk2
RB-Phos
A
r
B
C
D
A
r
B
C
D
E
s
<XML>
Diff
moves
product of r: C
deletes
product of r: B
inserts
species: E
product of r: E
reaction s
</XML>
• 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 r B
C
D
E s
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 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
S E Ssimulation 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
60. BiVeS
Integration
jvm network cmd
import de.unirostock.sems.bives.api.SBMLDiff;
[...]
SBMLDiff differ = new SBMLDiff (sbmlFileA, sbmlFileB);
differ.mapTrees ();
String graph = differ.getCRNGraphML ();
[...]
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 29
61. BiVeS
Integration
jvm network cmd
curl -d ’{
"get":
[
"documentType",
"xmlDiff"
],
"files":
{
"versionA":"http://your.db/path/to/versionA.sbml",
"versionB":"http://your.db/path/to/versionA.sbml"
}
}’ http://bives.server.tld
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 29
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
• input: 2 XML documents
• map unambiguos
nodes/subtrees
• propagate mapping up/down
• exploit further knowledge of
biological systems
A B
C
D E
A B
C
D E
A B
C
D E
Dec 4, 2013 SEMS | Martin Scharm, Ron Henkel, Dagmar Waltemath, Olaf Wolkenhauer 32