characterising differences between model versions

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

http://www.sbi.uni-rostock.de/team/single/martin-scharm/

http://sems.uni-rostock.de/waltemath




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)





CyclinCdc2 P

CyclinCdc2 P

Modeling the cell division...

John J Tyson, 1991

muell





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


John J Tyson, 1991

muell





Cyclin

Cdc2 P

Cyclin

Cdc2 P




Cyclin

Cdc2 P

Cyclin

Cdc2 P

Cdc25Cdc25∗

Mik1 Mik1∗

Wee1 Wee1∗

Quantitative analysis of a molecular model of mitotic control in Fission yeast


Cyclin

Cdc2 P

Cyclin

Cdc2 P


John J Tyson, 1991

muell





Cyclin

Cdc2 P

Cyclin

Cdc2 P




Cyclin

Cdc2 P

Cyclin

Cdc2 P

Cdc25Cdc25∗

Mik1 Mik1∗

Wee1 Wee1∗

Quantitative analysis of a molecular model of mitotic control in Fission yeast


Cyclin

Cdc2 P

Cyclin

Cdc2 P


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


muell




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





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





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





A

B

C D E

F

G

A

B

D H E

F

G

propagate this initial mapping into the rest of the tree





A

B

C D E

F

G

A

B

D H E

F

G

evaluate the mapping and identify inserts, deletes, updates, and moves





C

D

H E

communicate the differences to the user





<?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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28

Scharm et. al. BIOINFORMATICS 2015, accepted for publication




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





insertion <species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” />

Type: new nodeAffects: the reaction network

Intention: probably anextension of the model






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







<species name=“Gulcose-6-Phosphate” initialConcentration=“0.6” /><species name=“Glucose-6-Phosphate” initialConcentration=“0.6” />

Type: updated attribute

Reason: typo







<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




COMODICharacterising model differences

We’re building an ontology, because COmputational MOdels DIffer.

Change

Target

affected

Reason

hadReason

Intention

intended

Type

changeType

Entity

appliedTo




COMODICharacterising model differences

Entity

Node

ModelId

EntityIdentifier

Attribute

ModelName

EntityName

Text





is_a comodi:Changecomodi:changeType comodi:Insertioncomodi:affected comodi:ReactionNetworkcomodi:intended comodi:Extension

Masymos




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!?




SYSTEMS BIOLOGY

BIOINFORMATICS

ROSTOCKS E Ssimulation experiment management system

Thank you for your attention!

SEMS group

Dagmar WaltemathMartin ScharmMartin PetersMariam NassarFabienne LambuschOlaf Wolkenhauer

@SemsProject



https://twitter.com/semsproject




characterising differences between model versions

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