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Static analysis of protein protein interactions networks

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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


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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 =k1x1x2+k1x3 dt dx 2 =k1x1x2+k1x3 dt dx 3 =k1x1x2k1x3+ 2k2x3x3k2x4) dt dx vx 424 5 =k2(k3x4k3x5) dtx3k2x4+p4+x5 dx 5 =∙ ∙ ∙ dt . dxn =k1x1c2+k1x3 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