Jérôme Feret Laboratoire d'Informatique de l'École Normale Supérieure

Jérôme Feret

Description

SAS 2011 Formal model reduction Jérôme Feret Laboratoire d'Informatique de l'École Normale Supérieure INRIA, ÉNS, CNRS Friday, September the 16th

• laboratoire d'informatique de l'ecole normale


• abstract interpretation


• formal model


• msb4100014-e2 molecularsystemsbiology2005


• abstract semantics

Sujets

• Harmer
• Fontana
• Krivine
• Abstract interpretation

Informations

• Publié par: pefav
• Nombre de lectures: 17
• Langue: Français
• Poids de l'ouvrage: 4 Mo

Extrait

SAS 2011

Formal model reduction

Jérôme Feret Laboratoire d’Informatique de l’École Normale Supérieure INRIA, ÉNS, CNRS

Friday, September the 16th

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

Friday, September the 16th

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

Friday, September the 16th

Jérôme Feret

Signalling

4

Pathways

Eikuch, 2007

Friday, September the 16th

Jérôme Feret

Pathway

maps

Oda, Matsuoka, Funahashi, Kitano, Molecular Systems Biology, 2005

5

Friday, September the 16th

Differential models

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

−do not describe the structure of molecules; −combinatorial explosion:forces choices that are not principled; −a nightmare to modify.

Jérôme Feret

6

Friday, September the 16th

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

Friday, September the 16th

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

Friday, September the 16th

Several

d

So

G

b

a

Y 7

pi

semantics

E

R

Y 68

r

l

Y 48

r

Sh Interaction map

Jérôme Feret

Semantics

(qualititative

and/or

CTMC

9

quantitative)

can

be

defined.

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

Friday, September the 16th