1. 04/07/2007 M.L. Guerriero - AB 2007, Hagenberg, Austria 1 Modeling Static Biological Compartments with Beta-binders Maria Luisa Guerriero 1 Corrado Priami 1,2 Alessandro Romanel 1,2 1 ICT Dept., University of Trento, Italy 2 The Microsoft Research-University of Trento Centre for Computational and Systems Biology, Italy

2. 04/07/2007 2M.L. Guerriero - AB 2007, Hagenberg, Austria Outline of the talk Introduction to process algebra and Beta-binders Beta-binders extensions Compartments Localities and locality analysis An example Conclusions and future work

3. 04/07/2007 3M.L. Guerriero - AB 2007, Hagenberg, Austria Process algebras Languages for modeling concurrent systems System components are concurrent interacting processes Pairs of components synchronize by means of complementary input/output actions Examples: biochemical stochastic п-calculus, BioAmbients, Brane calculus, Beta-binders Tools and successful applications to biology

4. 04/07/2007 4M.L. Guerriero - AB 2007, Hagenberg, Austria Beta-binders: an overview Language of concurrent interacting processes with typed interaction sites The Abstraction: Biological entities Bio-processes Interaction Communication on typed sites Modification State change Biological compartments Compartments

5. 04/07/2007 5M.L. Guerriero - AB 2007, Hagenberg, Austria Beta-binders processes Body: internal behavior Interface: interactions Bio-process P Two levels of concurrency: bio-processes and pi-processes

6. 04/07/2007 6M.L. Guerriero - AB 2007, Hagenberg, Austria Beta-binders operations Input/output communications Operations on interfaces Merging/splitting of processes P|Q P’|Q’ intra P inter Q P’ Q’

7. 04/07/2007 7M.L. Guerriero - AB 2007, Hagenberg, Austria Operations on interfaces P P’ expose P P’ P’’ hideunhide

8. 04/07/2007 8M.L. Guerriero - AB 2007, Hagenberg, Austria Merging/splitting of processes PQ split R P join Q R

9. 04/07/2007 9M.L. Guerriero - AB 2007, Hagenberg, Austria Compartments: motivations Beta-binders forbids nesting of bio-processes Typing of sites virtual nesting Problem: Analysis of spatial distribution of objects B B’’ B’

10. 04/07/2007 10M.L. Guerriero - AB 2007, Hagenberg, Austria Compartments hierarchy i-components (internal to compartments) b-components (on membranes) 0 0,0 0,10,2 0,1,0

11. 04/07/2007 11M.L. Guerriero - AB 2007, Hagenberg, Austria Communications and movements A bio-process can interact with others residing in the same compartment or on its borders Movement of i-components among compartments: mediated by b-components

12. 04/07/2007 12M.L. Guerriero - AB 2007, Hagenberg, Austria Movement operations P Q P’ Q’ in move Q Q’ out move P P’ 0,0 0 0

13. 04/07/2007 13M.L. Guerriero - AB 2007, Hagenberg, Austria Localities Labels on bio-processes: uniquely identify them Labels on transitions: Which action is executed? Which bio-process executes it? In which compartment it occurs? B1B1 B2B2 B3B3 || 0 || 1 || 0 || 1

14. 04/07/2007 14M.L. Guerriero - AB 2007, Hagenberg, Austria Locality analysis Compartments locality relations on transitions φ i and φ j Analysis of labels κ( φ i ) and κ( φ j ) same-compartment κ( φ i ) = κ( φ j ) son-father κ( φ j ), m = κ( φ i ) father-son κ( φ i ), m = κ( φ j ) sub-compartment super-compartment Inter-box locality relation on transitions φ i and φ j Analysis of labels θ( φ i ) and θ( φ j ) same-box

15. 04/07/2007 15M.L. Guerriero - AB 2007, Hagenberg, Austria cAMP-signalling pathway in OSNs

16. 04/07/2007 16M.L. Guerriero - AB 2007, Hagenberg, Austria Conclusions Beta-binders: modeling, analysis and simulation of biological systems Compartments: representation of static biological compartments, membrane proteins, and movement of molecules across membranes Locality analysis: spatial relations between entities and between events

17. 04/07/2007 17M.L. Guerriero - AB 2007, Hagenberg, Austria Future work Dynamic compartments (creation, destruction, merging, movement of compartments, etc.) Distinction of transmembrane proteins, internal/external side of membranes Position of proteins within membranes Implementation within the Beta Workbench

18. 04/07/2007 18M.L. Guerriero - AB 2007, Hagenberg, Austria Thank you!