Static analysis of protein protein interactions networks

Jérôme Feret

Description

Niveau: Supérieur, Master
Master AIV Static analysis of protein-protein interactions networks Jérôme Feret Laboratoire d'Informatique de l'École Normale Supérieure INRIA, ÉNS, CNRS feret March 2012

• laboratoire d'informatique de l'ecole normale


• msb4100014-e2 molecularsystemsbiology2005


• x1 ·


• dt

Sujets

• Harmer
• Fontana
• Krivine

Informations

• Publié par: profil-mupheg-2012
• Nombre de lectures: 10
• Langue: English
• Poids de l'ouvrage: 9 Mo

Extrait

Master AIV

Static analysis of proteinprotein interactions networks

Jérôme Feret Laboratoire d’Informatique de l’École Normale Supérieure INRIA, ÉNS, CNRS ❤tt♣✿✴✴✇✇✇✳❞✐✳❡♥s✳❢r✴∼❢❡r❡t

March 2012

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

March 2012

Jérôme Feret

Signalling Pathways

3

Eikuch, 2007

March 2012

Pathway maps

March 2012

4

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

Jérôme Feret

Differential models

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

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

Jérôme Feret

5

March 2012

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

6

March 2012

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. 3. Quantitative semantics can be defined.

Jérôme Feret

7

March 2012

Jérôme Feret

Complexity walls

8

March 2012

Static analysis of reachable species (I/II)

Semifluid medium: the notion of individual is meaningless.

Design a static analysis to approximate the set of reachable species [VMCAI’08] which focuses on the relationships between the states of the sites of each agent:

This analysis is efficient, suitable to our problem, and accurate.

Jérôme Feret

9

March 2012

Static analysis of reachable species (II/II)

Applications: 1. check the consistency of a model [ICCMSE’07] 2. compute the properties to allow fast simulation [APLAS’07] 3. simplify models, 4. compute independent fragments of chemical species [PNAS’09, LICS’10,Chaos’10]

The analysis is complete (no false positif) for a significatif kernel of Kappa . [VMCAI’08]

Jérôme Feret

10

March 2012