Characterising differences between model versions
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SYSTEMS BIOLOGY
BIOINFORMATICS
ROSTOCKS E Ssimulation experiment management system
Characterising differencesbetween model versionsMARTIN SCHARM, DAGMAR WALTEMATHDepartment of Systems Biology & Bioinformatics, University of Rostock
http://sems.uni-rostock.de
e:Bio Status Seminar 2015University of Duisburg-Essen
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 1
Model EvolutionExample: Cell Cycle
Romond1999 Goldbeter1991 Tyson1991
Novak1993 Marlovits1998
Novak1995Novak1997
Moriya2011
Calzone2007
Novak1998
Tyson2001 Chen2000
Chen2004 Queralt2006 Vinod2011
Novak2001
Sriram2007
Csikasz-Nagy2006
Hatzimanikatis1999
Swat2004
Qu2003Ciliberto2003
mammalian R-point (G1/S-transition)
Srividyha2006
Mitotic exit
Budding Yeast
Not in biomodels database
minimal oscillatorNovak1995
Gardner1998
Ibrahim2008a Ibrahim2008b
Ibrahim2009Mitosis
Obeyesekere1997
Conradie2010
Obeyesekere1999
Bai2003
Aguda&Tang1999
Novak2004
Haberichter2007
(G-Phase)
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 2
Model EvolutionExample: Cell Cycle
Romond1999 Goldbeter1991 Tyson1991
Novak1993 Marlovits1998
Novak1995Novak1997
Moriya2011
Calzone2007
Novak1998
Tyson2001 Chen2000
Chen2004 Queralt2006 Vinod2011
Novak2001
Sriram2007
Csikasz-Nagy2006
Hatzimanikatis1999
Swat2004
Qu2003Ciliberto2003
mammalian R-point (G1/S-transition)
Srividyha2006
Mitotic exit
Budding Yeast
Not in biomodels database
minimal oscillatorNovak1995
Gardner1998
Ibrahim2008a Ibrahim2008b
Ibrahim2009Mitosis
Obeyesekere1997
Conradie2010
Obeyesekere1999
Bai2003
Aguda&Tang1999
Novak2004
Haberichter2007
(G-Phase)
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 2
Model EvolutionExample: Cell Cycle
CyclinCdc2 P
CyclinCdc2 P
Modeling the cell division...
John J Tyson, 1991
muell
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 3
Model EvolutionExample: 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
muell
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 3
Model EvolutionExample: 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
muell
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 3
Model EvolutionExample: 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
muell
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 3
BiVeS identifies differencesin versions of computational models
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 standadisedformats (currently: and )
• maps hierarchically structured content
• evaluates and communicates the differences
<XML>Diff
movesproduct of r: C
deletesproduct of r: B
insertsspecies: Eproduct of r: Ereaction s
</XML>
mapping
diff construction
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 4
BiVeS identifies differencesin versions of computational models
A
B
C D E
F
G
A
B
D H E
F
G
model version 1model version 2
list of species list of reactions
C + D = E D + H = E
take two versions of a computational model
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 5
BiVeS identifies differencesin versions of computational models
A
B
C D E
F
G
A
B
D H E
F
Gid=“species1” id=“species1”
connect entities which are for sure the same
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 6
BiVeS identifies differencesin versions of computational models
A
B
C D E
F
G
A
B
D H E
F
G
propagate this initial mapping into the rest of the tree
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 7
BiVeS identifies differencesin versions of computational models
A
B
C D E
F
G
A
B
D H E
F
G
evaluate the mapping and identify inserts, deletes, updates, and moves
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 8
BiVeS identifies differencesin versions of computational models
C
D
H E
communicate the differences to the user
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 9
BiVeS identifies differencesin versions of computational models
<?xml version="1.0" encoding="UTF-8" standalone="no"?><bives type="fullDiff">
<update/>
<delete>[...]<node id="6" oldChildNo="1"oldParent="../listOfModifiers[1]"oldPath="../listOfModifiers[1]/modifierSpeciesReference[1]"oldTag="modifierSpeciesReference" triggeredBy="5"/>
<attribute id="7" name="species"
oldPath="../modifierSpeciesReference[1]"oldValue="cdc2" triggeredBy="6"/>
</delete><insert>[...]<node id="12" newChildNo="2"newParent="../listOfReactants[1]"newPath="../listOfReactants[1]/speciesReference[2]"newTag="speciesReference"/>
<attribute id="13" name="species"
newPath="../speciesReference[2]"newValue="cdc2" triggeredBy="12"/>
<attribute id="14" name="metaid"newPath="../speciesReference[2]"newValue=" 818337" triggeredBy="12"/>
</insert>[...]
</bives>
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Scharm et. al. BIOINFORMATICS 2015, accepted for publication
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 10
What do these changes look like?
analysis of morethan 150 diffs
study ofmodifications
derivation ofa vocabulary
A
B
C D E
F
G
A
B
D H E
F
G
Change
affectedhadReason
intended
changeType
appliedTo
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 11
What do these changes look like?
insertion <species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” />
Type: new nodeAffects: the reaction network
Intention: probably anextension of the model
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 12
What do these changes look like?
insertion <species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” />
update <parameter name=“ka” value=“0.3” /><parameter name=“ka” value=“0.1” />
Type: updated attribute
Affects: the mathematical model
Intention: correctionReason: mismatch with publication
dcdc25dt =
ka×dimer_p×(total_cdc25−cdcs5p)Ka+total_cdc25−cdcs5p
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 12
What do these changes look like?
insertion <species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” />
update <parameter name=“ka” value=“0.3” /><parameter name=“ka” value=“0.1” />
<species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” /><species name=“Glucose-6-Phosphate” initialConcentration=“0.6” />
Type: updated attribute
Reason: typo
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 12
What do these changes look like?
insertion <species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” />
update <parameter name=“ka” value=“0.3” /><parameter name=“ka” value=“0.1” />
<species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” /><species name=“Glucose-6-Phosphate” initialConcentration=“0.6” />
deletion <reaction id=“r23”>...
</reaction>
Type: deletion of node and attributes
Affects: reaction network andmathematical model
Intention: simplification
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 12
COMODICharacterising model differences
We’re building an ontology, because COmputational MOdels DIffer.
Change
Target
affected
Reason
hadReason
Intention
intended
Type
changeType
Entity
appliedTo
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 13
COMODICharacterising model differences
Entity
Node
ModelId
EntityIdentifier
Attribute
ModelName
EntityName
Text
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 14
What do these changes look like?
is_a comodi:Changecomodi:changeType comodi:Insertioncomodi:affected comodi:ReactionNetworkcomodi:intended comodi:Extension
Masymos
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 15
SummaryQuestions we’d like to help answering
• How did my collaborator change our model?
• Did someone update the model that I retrieved from the database?
• Weird behaviour since the last update..!? Show me all versions that changedthe kinetics of reaction r23.
• Who changed reaction r23? When and why did they do that!?
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 16
SYSTEMS BIOLOGY
BIOINFORMATICS
ROSTOCKS E Ssimulation experiment management system
Thank you for your attention!
SEMS group
Dagmar WaltemathMartin ScharmMartin PetersMariam NassarFabienne LambuschOlaf Wolkenhauer
@SemsProject
http://sems.uni-rostock.de
September, 2015 COMODI | Martin Scharm, Dagmar Waltemath 17