Page 1
Tools and Methods for Improved Result Reproducibility in
Systems Biology (SEMS)
Department of Systems Biology and Bioinformatics
University of Rostock
Dagmar Waltemath, Martin Scharm, Ron Henkel, Olaf Wolkenhauer
e:Bio Kick-Off Meeting, 23-25 September 2013, Mainz
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 1
Page 2
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 2
Page 3
Reuse existing models.
0
20000
40000
60000
80000
100000
120000
0
100
200
300
400
500
600
700
800
900
Apr
-05
Jul-0
5
Oct
-05
Jan-
06
Apr
-06
Jul-0
6
Oct
-06
Jan-
07
Apr
-07
Jul-0
7
Oct
-07
Jan-
08
Apr
-08
Jul-0
8
Oct
-08
Jan-
09
Apr
-09
Jul-0
9
Oct
-09
Jan-
10
Apr
-10
Jul-1
0
Oct
-10
Jan-
11
Apr
-11
Jul-1
1
Oct
-11
Jan-
12
Nu
mb
er o
f A
nn
ota
tio
ns
Nu
mb
er o
f M
od
els
Models
Annotation
+ 140.811 derived models
(Models in BioModels Database; Figure courtesy Ron Henkel)
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 3
Page 4
Reproduce published results.
“[..] in Biomodels database the model BIOMD0000000139 and
BIOMD0000000140 are two different models and they are supposed to show
different results. Unfortunately simulating them [..] gives same result for
both the models. [..] “ (Quote: arvin mer on sbml-discuss)
(Figures produced in COPASI)
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 4
Page 5
SEMS – Improving result reproducibility
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 5
"Quantitative models will be only as useful as
their access and reuse is easy for all scientists”
(Nicolas Le Novère, 2006)
Page 6
Standard representation formats
(Fig. adapted from: Courtot, Waltemath et al. Nature MSB, 2011)
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 6
Page 7
Standard representation formats
NuML
SBRML
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 7
(Fig. adapted from: Courtot, Waltemath et al. Nature MSB, 2011)
Page 8
Standard representation formats
MAMO
NuML
SBRML
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 8
(Fig. adapted from: Courtot, Waltemath et al. Nature MSB, 2011)
Page 9
Data links
MAMO
NuML
SBRML
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 9
(Fig. adapted from: Courtot, Waltemath et al. Nature MSB, 2011)
Page 10
Data links
MAMO
NuML
SBRML
(Fig. adapted from: Courtot, Waltemath et al. Nature MSB, 2011)
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 10
Page 11
Project goals
1. Specify and establish a standard for the description of
simulation experiments (SED-ML) Waltemath et al. BMC Sys Biol (2011)
2. Develop methods for simulation management with focus on
model provenance Waltemath et al. Bioinformatics (2013)
3. Establish links between model-related data on storage level Henkel et al. INFORMATIK2012 (2012)
4. Promote reproducible science
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 11
Page 12
Standard representation of simulation experiments
http://sed-ml.org/
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 12
Page 13
Model provenance
(Figure courtesy Martin Scharm)
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 13
Page 14
Model provenance: BiVeS & BudHat
http://budhat.sems.uni-rostock.de
VANTED
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 14
Page 15
ModelGraphs:Linking model-related data
(Fig.: Henkel et al. INFORMATIK2012 (2012))
(Figure courtesy Ron Henkel, COMBINE2013)
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 15
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623Interpro:
IPR006670
isV
ers
ion
Of
isV
ers
ion
ha
sP
art
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isV
ers
ion
Of
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623Interpro:
IPR006670
isV
ers
ion
Of
isV
ers
ion
ha
sP
art
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isV
ers
ion
Of
Document
SEDML
Modelrefere
nceOutput
Datagenera
torSimulation Task
Variable
Variable
Document
Tyson_1991
C2 CP
time
environment
isDescribedBy Pubmed:
1831270
time timeCPC2 CP C2
is_connected is_connected
is_mapped_to
is_connected
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
http://sems.uni-rostock.de/projects/morre/
Page 16
ModelGraphs:Linking model-related data
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 16
Document
Tyson1991
Cell Cycle 6
var
C2 pM CellReaction3 CP
Uniprot:P04551 Uniprot:P04551 GO:0005623Interpro:
IPR006670
isV
ers
ion
Of
isV
ers
ion
ha
sP
art
is
asProduct
asReactant isContainedIn
Pubmed:
1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code:
3.1.3.16
isV
ers
ion
Of
Document
SEDML
Modelrefere
nceOutput
Datagenera
torSimulation Task
Variable
Variable
Document
Tyson_1991
C2 CP
time
environment
isDescribedBy Pubmed:
1831270
time timeCPC2 CP C2
is_connected is_connected
is_mapped_to
is_connected
SBO:
Ontology
SBO:0000
SBO:544 SBO:236SBO:231
isA
SBO:064 SBO:545SBO:004 SBO:003
Model
Publication
Annotation
Person
Simulation
Show me models by Tyson,
dealing with the Cell Cycle and
simulating concentration of cdc2!
Page 17
Summary
24.09.2013 e:Bio SEMS | sems.uni-rostock.de | Dagmar Waltemath 17
track development
store retrieve
rank
Retrieval
Ranking
Δ
Δ
Version 1
Version 2
latest
Version Control
DocumentTyson1991 Cel
l Cycle 6
var
C2 pMCel
l
Reaction
3
CP
Uniprot:P04551
Uniprot:P04551
GO:00056
23
Interpro
: IPR006670
isV
ersi
on
Of
isV
ersi
on
has
Par
t
is
Pubmed:1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code: 3.1.3.
16
isV
ersi
on
Of
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation
Task
Variable
Variable
Docume
nt
Tyson_19
91
C2 CP
time
environ
ment
isDescribedByPubm
ed:183127
0
Pubmed:
1831270
time timeCPC2 CP C2
DocumentTyson1991 Cel
l Cycle 6
var
C2 pMCel
l
Reaction
3
CP
Uniprot:P04551
Uniprot:P04551
GO:00056
23
Interpro
: IPR006670
isV
ersi
on
Of
isV
ersi
on
has
Par
t
is
Pubmed:1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code: 3.1.3.
16
isV
ersi
on
Of
DocumentTyson1991 Cel
l Cycle 6
var
C2 pMCel
l
Reaction
3
CP
Uniprot:P04551
Uniprot:P04551
GO:00056
23
Interpro
: IPR006670
isV
ersi
on
Of
isV
ersi
on
has
Par
t
is
Pubmed:1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code: 3.1.3.
16
isV
ersi
on
Of
DocumentTyson1991 Cel
l Cycle 6
var
C2 pMCel
l
Reaction
3
CP
Uniprot:P04551
Uniprot:P04551
GO:00056
23
Interpro
: IPR006670
isV
ersi
on
Of
isV
ersi
on
has
Par
t
is
Pubmed:1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code: 3.1.3.
16
isV
ersi
on
Of
Docume
nt
Tyson_19
91
C2 CP
time
environ
ment
isDescribedByPubm
ed:183127
0
Pubmed:
1831270
time timeCPC2 CP C2
DocumentTyson1991 Cel
l Cycle 6
var
C2 pMCel
l
Reaction
3
CP
Uniprot:P04551
Uniprot:P04551
GO:00056
23
Interpro
: IPR006670
isV
ersi
on
Of
isV
ersi
on
has
Par
t
is
Pubmed:1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code: 3.1.3.
16
isV
ersi
on
Of
DocumentTyson1991 Cel
l Cycle 6
var
C2 pMCel
l
Reaction
3
CP
Uniprot:P04551
Uniprot:P04551
GO:00056
23
Interpro
: IPR006670
isV
ersi
on
Of
isV
ersi
on
has
Par
t
is
Pubmed:1831270
Kegg Pathway
sce04111
isDescribedBy
is
EC-Code: 3.1.3.
16
isV
ersi
on
Of
Docume
nt
Tyson_19
91
C2 CP
time
environ
ment
isDescribedByPubm
ed:183127
0
time timeCPC2 CP C2
Storage
Document
SEDML
Modelrefere
nce
Output
Simulation
Task
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation
Task
Variable
Variable
Document
SEDML
Modelrefere
nce
Output
Datagenera
tor
Simulation
Task
http://sbml.org
Page 18
Thank you for your attention!
SEMS group
Martin Scharm
Martin Peters
Markus Wolfien
Rebekka Alm
Olaf Wolkenhauer
Associated member
Ron Henkel
Collaborators
Falk Schreiber (IPK Gatersleben)
Christian Rosenke (University of Rostock)
Jon Olav Vik (UMB)
Jonathan Cooper (University of Oxford)
Tommy Yu (University of Auckland)
COMBINE
SED-ML Editors
biomodels.net
http://sems.uni-rostock.de/
@SemsProject HERMES-
Forschungsförderung
der Universität Rostock