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Biology & computing

Biology & computing. Franck Delaplace IBISC – Evry University - Genopole BERDER 2012. Synthetic Biology in a Nutshell. Multi disciplinary approach design of synthetic bio-systems Engineering principles. Design  Assembly of BIOBRICKS. Kwok -Nat. 463 Jan. 2010. Modeling.

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Biology & computing

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  1. Franck Delaplace - Berder 2012 Biology & computing Franck Delaplace IBISC – Evry University - Genopole BERDER 2012

  2. Franck Delaplace - Berder 2012 Synthetic Biology in a Nutshell • Multi disciplinary approach • design of synthetic bio-systems • Engineering principles Design  Assembly of BIOBRICKS Kwok -Nat. 463 Jan. 2010

  3. Franck Delaplace - Berder 2012 Modeling Design

  4. Franck Delaplace - Berder 2012 What I cannot compute, I cannot understand … Computing = Understanding HOPE SO ! <3

  5. Franck Delaplace - Berder 2012 computation Biology Life as model of computation Bio-inspired computation Biology Computing with Life Synthetic Biology Programming Life Systems biology computation model as a model of Life

  6. Franck Delaplace - Berder 2012 Bio-inspired algorithms & models Life as model of computation

  7. Franck Delaplace - Berder 2012 Bio-Inspired algorithms • Computation Framework • For a large class of problems • Meta heuristic • For complex problems • Intractable  NP complete • IA problems (Design) • Common Features • Population, Society • Local operations • Global evaluation • Randomness

  8. Franck Delaplace - Berder 2012 Genetic algorithm - Bridge Design Darwinian Paradigm Funes, Pablo, Lapat, Louis and Pollack, Jordan B. EvoCAD: Evolution-Assisted Design. Artificial Intelligence in Design'00  Agent = Genome coding for a bridge

  9. Franck Delaplace - Berder 2012 Bio-Inspired models Turing machine = “common ancestor” • New computing model • Alternative computation medium • New computing rules • Computational power • Turing universality: Simulation of a computer (universal Turing machine) • Massive parallelism :combinatorial resolution of NP complete problems

  10. Franck Delaplace - Berder 2012 Example Membrane computing • P-System • Non determinism • Evolution strategy  maximal parallel • Application • Sorting • NP complete problem (TSP) • Verification of cryptography protocol Skin Membrane Rules Objects

  11. Franck Delaplace - Berder 2012 Systems biology computation as a model of biological processes

  12. l'une des propriétés fondamentales qui caractérisent tous les êtres vivants sans exception : celle d'être des objets doués d'un projet qu'à la fois ils représentent dans leurs structures et accomplissent par leurs performances . [..] Il est indispensable de la reconnaître comme essentielle à la définition même des êtres vivants. [..] que nous appellerons la téléonomie Franck Delaplace - Berder 2012 computation-inspired framework « De toute évidence, la cohérence fonctionnelle d'une machine chimique aussi complexe, et en outre autonome, exige l'intervention d'un système cybernétique gouvernant et contrôlant l'activité chimique en de nombreux points. » (p. 59) • “Cybernétiquemoléculaire” • Circuit / Network explanatory framework of biological process • Logical Network (R.Thomas)

  13. Franck Delaplace - Berder 2012 Formal models • Discrete dynamics • State based • Formal property analysis • Safety • Reachability / invariance • Explanatory framework • Formalization of Biological process • Phenotype = molecular signature  equilibria Transition State State

  14. Franck Delaplace - Berder 2012 Example - Automata based model a b c 101 111 a b 001 011 100 110 c a = NOT c b = a c = NOT b 000 010 Specification Dynamics

  15. Franck Delaplace - Berder 2012 Synthetic biology Programming/designing living organism

  16. Franck Delaplace - Berder 2012 Design-manufacturing  compilation main(){ Printf (“Hello World”); } Program Compilation Execution Computer SB function Synthesis Synthetic Biology

  17. Franck Delaplace - Berder 2012 CAD Environment (ideal) Overview High level Program Low level Program Sequence Interface Translator/ Compiler Validation/ Optimization Synthesis Parts Dedicated Specification Genetic Engineering Database Dynamics Analysis Safety Security Checking Simulator Trace Report Integrated view from the current states of art

  18. Franck Delaplace - Berder 2012 Compilation principles in a nutshell MEMORY + LDC 3, R5 ADD R5,R6,R7 LDC 4,R2 LD &K, R1 / III LD V,Rx ST V,Ry LDC 3, R5 DIV R4,R3,R6 MUL R2,R1,R4 REGISTER LD R3, &J J * LD R3, &J MUL R2,R1,R4 ADD R5,R6,R7 UAL IV K LDC 4,R2 LD &K, R1 OP R1,R2,R3

  19. Franck Delaplace - Berder 2012 Languages for SB  Structural description (GEC [Pedersen,Plotkin]) r0040:prom;b0034:rbs;c0040:prc;X:ter • Program =sequence description • Usual in language & CAD Env. • Genocad, GEC, Kera • Clotho, Eugène, Tinker Cell, … • Grammar rules = guide of design • Structural description • Low level (DNA sequence) R0040 c0040 b0034 X (Genocad[Peccoud] ) GENE CODING SEQ PROM START RBS PROT STOP

  20. Franck Delaplace - Berder 2012 Structural vs. behavioral description Hardware Description Language Verilog - VHDL • Structure • component assembly description • Low level of description • Back end • Behavior/function • Process design • Functional  safety • High level of description • Specification/document Generate Oil Y when X X Y r0040:prom;b0034:rbs;.. ATG|AAA|TTG|… Toy example

  21. Franck Delaplace - Berder 2012 Compilation  Part assembly = behavior assembly • Component description = behavior description • Bio system design = behavior description • The program describes the expected “function” • The issue is to define a compilation method assembling parts such that the behavior of the assembly is “similar” to the behavior of the designed function. • Problem - Reliability  guaranty on the assembly • i.e. formal guaranty that each step is correct w.r.t. to the behavioral “similarity”. Correct translation (compilation) ? Prom X Y b0034 b0015 X Y Program Assembly

  22. Franck Delaplace - Berder 2012 Behavior compilation for SB - 2 possible ways Dessinemoi un canard ! State = Situation Axioms Behavior of components Event-driven transition Proof Theorem Behavior ofthe function State = Situation

  23. Franck Delaplace - Berder 2012 Model & theory in logic Is a formula true ? Model Theory Completeness Correction Interpretation Deduction system ()

  24. Franck Delaplace - Berder 2012 Correction of the assembly Correction of assembly = observational behavior inclusion Compilation = Proof  find a behavior assembly s.t. the behavior of the designed function is included Part A Part B + AATGCGTTTATAGCCCCATGG.. AATTGGAAGCC

  25. Franck Delaplace - Berder 2012 Remarks • Functional/behavioral programming • 1 function  n structures – e.g. inhibition - • Document function  Safety analysis capability • Proof framework • Safe design  formal method + safety analysis • Functional/qualitative description  Specification, resolution principles • Quantitative description  Strategy of the resolution, tuning • Hierarchy of the components Organization for organisms • Functionality • Inter-operability • GUBS project - Adrien Basso Blandin – Franck Delaplace • Behavioral language • Compiler

  26. Franck Delaplace - Berder 2012 Synbiotic : Tower of languages GUBS Nature 434: Basu S & al.

  27. Franck Delaplace - Berder 2012 Conclusion Life as model of computation Bio-inspired • Function • Process computation Biology Computing with Life Synthetic Biology Programming Life Behavioral Language for synthetic biology Systems biology computation model as a model of Life

  28. Franck Delaplace - Berder 2012 l Thank you !

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