Exact and automatic reduction of rule based models

Exact and automatic reduction of rule based models

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MFPS XXVII Exact and automatic reduction of rule-based models Jérôme Feret Laboratoire d'Informatique de l'École Normale Supérieure INRIA, ÉNS, CNRS Thursday, May the 26th

  • laboratoire d'informatique de l'ecole normale

  • abstract interpretation

  • msb4100014-e2 molecularsystemsbiology2005

  • oda etal

  • abstract semantics


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Publié par
Ajouté le 19 juin 2012
Nombre de lectures 33
Langue English
Signaler un abus
MFPS XXVII
Exact and automatic reduction of rule-based models
Jérôme Feret Laboratoire d’Informatique de l’École Normale Supérieure INRIA, ÉNS, CNRS
Thursday, May the 26th
Joint-work with...
Walter Fontana Harvard Medical School
Jérôme Feret
Russ Harmer Harvard Medical School
Vincent Danos Edinburgh
2
Ferdinanda Camporesi Bologna / ÉNS
Jean Krivine Paris VII
Thursday, May the 26th
Overview
1.Context and motivations
2. Handmade ODEs 3. Abstract interpretation framework 4. Kappa 5. Concrete semantics 6. Abstract semantics 7. Conclusion
Jérôme Feret
3
Thursday, May the 26th
Jérôme Feret
Signalling
4
Pathways
Eikuch, 2007
Thursday, May the 26th
Jérôme Feret
Pathway
maps
Oda, Matsuoka, Funahashi, Kitano, Molecular Systems Biology, 2005
5
Thursday, May the 26th
Differential models
dxtd1= −k1x1x2+k1x3 ddxt2= −k1x1x2+k1x3 ddxt3=k1x1x2k1x3+2k2x3x3k2x4 dxdt4=k2x23k2x4+v4x5(k3x4k3x5) p4+x5 dx 5=∙ ∙ ∙ dt . n= −k1x1c2+k1x3 dx dt
do not describe the structure of molecules; combinatorial explosion:forces choices that are not principled; a nightmare to modify.
Jérôme Feret
6
Thursday, May the 26th
A gap between two worlds
Two levels of description: 1. Databases of proteins interactions in natural language + documented and detailed description + transparent description cannot be interpreted 2. ODE-based models + can be integrated opaque modelling process, models can hardly be modified there are also some scalability issues.
Jérôme Feret
7
Thursday, May the 26th
Rule-based approach
We use site graph rewrite systems
1. The description level matches with both the observation level and the intervention level of the biologist.
We can tune the model easily. 2. Model description is very compact.
Jérôme Feret
8
Thursday, May the 26th
Several
d
So
G
b
a
Y7
semantics
E
r Rl
Y68 Y48 pi
r
Sh Interaction map
Jérôme Feret
Semantics
(qualititative and/or quantitative) can be defined.
CTMC
9
dxdt1= −k1x1x2+k1x3 ddxt2= −k1x1x2+k1x3 dx3=k1x1x2k1x3+2k2x3x3k2dxdttddx4=k2x23k2x4+vp44+xx55− (k3x4k3x5)x4 5=∙ ∙ ∙ dt . xdtdn= −k1x1c2+k1x3 ODEs
Thursday, May the 26th
Several
d
So
G
b
a
Y7
semantics
E
r Rl
Y68 Y48 pi
r
Sh Interaction map
Jérôme Feret
Semantics
(qualititative and/or quantitative) can be defined.
CTMC
10
xdtd1= −k1x1x2+k1x3 ddxt2= −k1x1x2+k1x3 dx3=k1x1x2k1x3+2k2x3x3k2x4) dt dxdt4=k2x32k2x4+pv44+xx55− (k3x4k3x5) dx5 =∙ ∙ ∙ dt . xdtdnk1x1c2+k1x3 = − ODEs
Thursday, May the 26th