(Towards a) Modelling Platform for Biological Systems
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Transcript of (Towards a) Modelling Platform for Biological Systems
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(Towards a) Modelling Platform for Biological Systems
Marian Gheorghe
University of Sheffield
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What the method does
Use computer science models & concepts and software engineering approach & tools
• Formal model – membrane systems: modular and uses “natural” approach (Nott & Sheff)
• Formal analysis + learning mechanisms;
• Automated design – structure and parameters
Simulations, verifications, system restructuring and design
FJ Romero-Campero, J Twycross, M Camara, M Bennett, M Gheorghe, N Krasnogor, IJFCS, 2009FJ Romero-Campero, N Krasnogor, CiE 2009 F Bernardini,M Gheorghe,FJ Romero-Campero,N Walkinshaw,WMC 2007
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“Natural” modelling -Membrane computing
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Membranes
Objects
Regions
Cell Membrane (P) system
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What is a (basic) membrane system
A membrane system is a computing model consisting of • chemicals are modelled as symbols or strings, called abstract objects• regions (compartments) contain multisets of objects and other membranes• rules are associated to regions• system evolves through transitions
http://ppage.psystems.eu/The Oxford Handbook of Membrane Computing – To appear: 24/12/2009
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Rules and computation
(a) transformation: [a → x]c complex formation/dissociation; activators/inhibitors
(b) communication: a[]c → [a]c, [a]c → a[]c ; symport, antiport
(c) cell division: [a]c → [b]c [d]c
(d) cell differentiation: [a]c → [b]e
(e) cell death: [a]c → ; a, b, d, x – multisets
• Execution strategies
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Modelling molecular interactions
Biochemistry P systemsCompartment Region
Molecules Objects (symbols, strings)
Molecular population Multiset of objects
Biochemical transformations Various rules
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Gene regulatory network - P system model
Lac operon in E coli: Hlavacek, Savageau, 1995
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Simulations
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Invariants of the model
Initial values:
gene = 1, act = n, rep = m; where n, m either 0 or 10
others = 0
P-invariants
PIPE: http://pipe2.sourceforge.net
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Property inference
Daikon tool:
Reverse-engineer specifications from software systems – as preconditions, postconditions and invariants (Ernst et all, 2001) – formal analysis and testing
In the context of biological data, it automatically infers invariants to:
• confirm the model behaves as it should - obvious invariants
• indicate faults – anomalous invariants
• suggest novel relationships
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Daikon: Pre-, post-conditions and invariants
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Daikon: Pre-, post-conditions and invariants
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Daikon: Pre-, post-conditions and invariants
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Daikon: Pre-, post-conditions and invariants
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Formal verification - model checking
Use PRISM –
• Probability that the mRNA or the protein is within/under/over some limits
• Monotonic increase of some products
• Relevant properties
M Kwiatkowska et al 2002
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P systems in PRISM
P system model
PRISM code
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Invariants checking – positive regulation
… more likely rna’s between 0 and 15, proteins between 0 and 150
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Check relationships
Relationships between the number of repressors and rna and protein molecules
P(prot>rep) P(rna>rep)
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Conclusions and further developments
• Integrated engineering approach
• P systems – modelling approach for molecular interactions;
modular and “natural”
• Automated design
• Property inference
• Formal verification
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Thanks?