Exact and automatic reduction of rule based models

Jérôme Feret

Description

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

Sujets

• Harmer
• Fontana
• Krivine
• Abstract interpretation

Informations

• Publié par: pefav
• Nombre de lectures: 34
• Langue: English
• Poids de l'ouvrage: 4 Mo

Extrait

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

 dx td 1 = −k 1 ∙x 1 ∙x 2 +k −1 ∙x 3 d d x t 2 = −k 1 ∙x 1 ∙x 2 +k −1 ∙x 3 d d x t 3 =k 1 ∙x 1 ∙x 2 −k −1 ∙x 3 +2∙k 2 ∙x 3 ∙x 3 −k −2 ∙x 4   dx dt 4 =k 2 ∙x 2 3 −k 2 ∙x 4 + v 4 ∙x 5 (k 3 ∙x 4 −k −3 ∙x 5 ) − p 4 +x 5 dx 5 =∙ ∙ ∙ dt .   n = −k 1 ∙x 1 ∙c 2 +k 1 ∙x 3 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

Y 7

semantics

E

r R l

Y 68 Y 48 pi

r

Sh Interaction map

Jérôme Feret

Semantics

(qualititative and/or quantitative) can be defined.

CTMC

9

 dx dt 1 = −k 1 ∙x 1 ∙x 2 +k −1 ∙x 3 d d x t 2 = −k 1 ∙x 1 ∙x 2 +k −1 ∙x 3 dx 3 =k 1 ∙x 1 ∙x 2 −k −1 ∙x 3 +2∙k 2 ∙x 3 ∙x 3 −k −2 ∙   dx dt td dx 4 =k 2 ∙x 2 3 −k 2 ∙x 4 + v p 4 4 ∙ + x x 5 5 − (k 3 ∙x 4 −k −3 ∙x 5 ) x 4 5 =∙ ∙ ∙ dt .   xd td n = −k 1 ∙x 1 ∙c 2 +k −1 ∙x 3 ODEs

Thursday, May the 26th

Several

d

So

G

b

a

Y 7

semantics

E

r R l

Y 68 Y 48 pi

r

Sh Interaction map

Jérôme Feret

Semantics

(qualititative and/or quantitative) can be defined.

CTMC

10

 x dt d 1 = −k 1 ∙x 1 ∙x 2 +k −1 ∙x 3 d d x t 2 = −k 1 ∙x 1 ∙x 2 +k −1 ∙x 3 dx 3 =k 1 ∙x 1 ∙x 2 −k −1 ∙x 3 +2∙k 2 ∙x 3 ∙x 3 −k −2 ∙x 4 )  dt  dx dt 4 =k 2 ∙x 3 2 −k 2 ∙x 4 + p v 4 4 ∙ +x x 5 5 − (k 3 ∙x 4 −k −3 ∙x 5 ) dx 5 =∙ ∙ ∙ dt .   x dt d n k 1 ∙x 1 ∙c 2 +k −1 ∙x 3 = − ODEs

Thursday, May the 26th