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Microsoft Research Faculty Summit 2007
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Colonies Of Colonies Of Synchronizing Agents:Synchronizing Agents:Molecules, Cells, Molecules, Cells, And TissuesAnd TissuesMatteo Cavaliere – MSR – UNITN CoSBi (Trento, Italy)Giuditta Franco - University of Verona, ItalyNatasha Jonoska – University of South FloridaSean Sedwards – MSR – UNITN CoSBi (Trento, Italy)
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Model Model
intuitiveness, intuitiveness, transparency, transparency,
scalability, scalability, composability, composability,
expressivity, simplicity, expressivity, simplicity, analysability …analysability …
MotivationMotivation
RealityReality
Formalization…Formalization…
Petri nets process algebraPetri nets process algebra
ODE statistical mechanicsODE statistical mechanics
rewriting automatarewriting automata
Formalization…Formalization…
Petri nets process algebraPetri nets process algebra
ODE statistical mechanicsODE statistical mechanics
rewriting automatarewriting automata
UnderstandiUnderstandingngand and
PredictionPrediction
AnalysisAnalysisInterpretatiInterpretationon
Efficient simulation…Analytical solution…
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Role Of Computer ScienceRole Of Computer Science
ComputationComputationalal
ModelModel
MathematicMathematicalal
modelmodelExperimentsExperiments CSCS
Intuition
IntuitioIntuitionn
The problem:Human intuition is the limiting step
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MathematicMathematicalal
ModelModelCSCS
ComputationComputationalal
ModelModelExperimentsExperiments AnalysisAnalysis
Inference
Role Of Computer ScienceRole Of Computer Science
The goal:Formalise and automate
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A Membrane SystemA Membrane System
a a b
c c a
b
a a b + a a + ca b
a + b c
b + c b + a
hierarchical system of compartments with membranes
multisets of floating objects local to regions
local ‘chemical’ rules based on multiset rewriting
system environment
a b
multisets of objects attached to membranes plus transport rules
a + b c
c
b
conflicts between rules areresolved non-deterministically
0
1
23
4
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Knee InjuryKnee InjuryThe important actors:B', C' lining cellsaltered hyaluronan (HA) molecules h’activated macrophages D’
Knee tissue after injury
Knee tissue in healthy state
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Knee Injury ModelKnee Injury ModelRegular cell turnover of the system in a homeostatic state
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Knee Injury ModelKnee Injury Model
G. Franco, N. Jonoska, B. Osborn, A. Plaas, Knee Joint Injury and Repair Modeled by Membrane Systems, Biosystems, to appear.
Gravity signals s (injury)instigates a cascade ofbiochemical interactions(the healing process)
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Computational IssuesComputational Issues
Formal description andanalysis of the healing process
Confirmed structural importance of hyaluronan for tissue repair
Analysis using techniques from symbolic dynamicsThe system is non-deterministic
Represents lack of knowledge and innate stochasticityCreates complexity for analysis
Potential parallelization (e.g., on a cluster)
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Generalized version of Membrane SystemsPopulation of enclosed regions (agents) in 3D containing objects
Internal rewriting rules (chemistry)
Pairwise synchronization rulesSynchronized rewriting (synchronized chemistry)
Passage of objects (molecules) between regions
Plus movement, division and deletion rules
Agents may represent molecules or cellsA colony may be a tissue or a solution
Colonies Of Synchronizing Colonies Of Synchronizing AgentsAgents
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Agents (cells) contain multisets of objects (molecules) and are acted upon by rules (reactions)
chemistry [a,b] [c,d]synchronization[a] [b] [c] [d]deletion [a] λ
Colonies Of Synchronizing Colonies Of Synchronizing AgentsAgents
a bb a a
b b a a c
a b c c
10 100 26
Number of agents of type
Initial contents of agent
movement [a] (,,)[b]division [a] [c] [d]
Having space, movement and division allows us to model complex spatio-temporal behaviour and structures, e.g., morphogenesis, quorum sensing…
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[a,b,c,a] → [b,a]
a b c
b c
a b
b
a b c
b a
a b c
b c
a b
b
b a
b
Internal Rules Internal Rules
Intracellular mechanisms, e.g., chemistry
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Synchronization Rules Synchronization Rules
[a,b,c] [c,c] [a,b,c] [c,c] → [a,a] [c,b]→ [a,a] [c,b]
a b c
b c
a b
b
a b c
b a
a b
b
a a
b a
a b c
b b
Intercellular mechanisms, e.g., signalling
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Evolution Of ColoniesEvolution Of Colonies
Global behaviour of a colony is obtained using just internal rules + synchronization rules
Overall behaviour is more complex than the sum of the individual components
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Robustness Of ColoniesRobustness Of Colonies
Robust behaviour is biologically important
A robust colonyThe behaviour does not change critically if one or more agents cease to exist or if one or more rules stop working
There are (efficient) algorithms to check if a colony is robust*
M. Cavaliere, R. Mardare, S. Sedwards, Colonies of Synchronizing Agents: An Abstract Model of M. Cavaliere, R. Mardare, S. Sedwards, Colonies of Synchronizing Agents: An Abstract Model of Intracellular and Intercellular Processes, Int. Work. on Automata for Cellular and Molecular Intracellular and Intercellular Processes, Int. Work. on Automata for Cellular and Molecular Computing, Budapest, 2007.Computing, Budapest, 2007.
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Why Simulate?Why Simulate?
Modelling Behavioural Need topower complexity simulate
maximal……minimal
Difficulty of deciding properties
(analysability)
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Simulation ComplexitySimulation Complexity
Complexity of each step of a stochastic simulation
Membrane system with M reactions: O(M)CSA with N agents, no synchronization: O(NM)CSA with N agents, space and synchronization: O(N2M)
Optimised algorithm: O(NM)
Optimised and distributed algorithm: O(NM½)
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ProspectsProspects
More complex biological modelsE.g., immune system, cell cycle, evolution
Model checking algorithms
Distributed implementation of CSAs
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Thank You For Your Thank You For Your AttentionAttention
Contributors:
Matteo Cavaliere – MSR – UNITN CoSBi (Trento, Italy)
Sean Sedwards – MSR – UNITN CoSBi (Trento, Italy)
Giuditta Franco - Department of Computer Science, University of Verona, Italy
Natasha Jonoska – Department of Computer Science, University of South Florida
Barbara Osborn - Department of Internal Medicine, University of South Florida
Anna Plaas - Department of Internal Medicine, University of South Florida
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© 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation.
Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN
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