Scalable agent-based simulations

A talk I gave at the end of my Nuffield project a few years back. I've been working on scientifically sound blood clotting simulation with a nice 3d visualisation on top.

Transcript

1. Scalable agent-based simulations: a blood clotting demonstrator Results of the 8 week Nuffield project Gregory Goltsov
2. What is blood clotting
3. What is hemostasis
4. Physical modelling of clot formation Xu Z, Lioi J, Mu J, Kamocka MM, Liu X, Chen DZ, Rosen ED, & Alber M (2010). A multiscale model of venous thrombus formation with surface-mediated control of blood coagulation cascade. Biophysical journal, 98 (9), 1723-32 PMID: 20441735
5. Physical modelling of clot formation Xu Z, Lioi J, Mu J, Kamocka MM, Liu X, Chen DZ, Rosen ED, & Alber M (2010). A multiscale model of venous thrombus formation with surface-mediated control of blood coagulation cascade. Biophysical journal, 98 (9), 1723-32 PMID: 20441735
6. Pathology Thromboembolism Formation in a blood vessel of a clot (thrombus) that breaks loose and is carried by the blood stream to plug another vessel. Pulmonary embolism Blockage of the main artery of the lung.
7. Pathology Thromboembolism Formation in a blood vessel of a clot (thrombus) that breaks loose and is carried by the blood stream to plug another vessel. Pulmonary embolism Blockage of the main artery of the lung. Aspirin
8. Aspirin Everyone aged over 45 should consider a small daily dose of aspirin to help protect themselves against heart disease and cancer “
9. Clotting modelling: ODEs
10. Clotting modelling: ODEs Great attention to uid dynamics
11. Clotting modelling: ODEs Great attention to uid dynamics Not so much to internal representation of platelet
12. Clotting modelling: ODEs Great attention to uid dynamics Not so much to internal representation of platelet Probabilistic representation of space
13. Platelet
14. Vs
17. Clotting modelling: agents
18. Clotting modelling: agents Agent-based simulation — platelets are agents.
19. Clotting modelling: agents Agent-based simulation — platelets are agents. Each individual platelet has its own behaviour.
20. Clotting modelling: agents Agent-based simulation — platelets are agents. Each individual platelet has its own behaviour. Explicit account of space — allows for near-neighbour interactions.
23. What’s been done
25. TUNA TECHNOLOGY UNDERPINNING N A N O T E C H ASSEMBLERS
26. TUNA TECHNOLOGY UNDERPINNING N A N O T E C H ASSEMBLERS
27. TUNA TECHNOLOGY UNDERPINNING N A N O T E C H ASSEMBLERS CoSMoS C O M P L E X S Y S T E M S MODELLING & SIMULATION
28. TUNA TECHNOLOGY UNDERPINNING N A N O T E C H ASSEMBLERS CoSMoS C O M P L E X S Y S T E M S MODELLING & SIMULATION +
29. TUNA TECHNOLOGY UNDERPINNING N A N O T E C H ASSEMBLERS CoSMoS C O M P L E X S Y S T E M S MODELLING & SIMULATION + CrISp CENTRE FOR RESEARCH IN SYSTEMS PATHOLOGY
30. What is inside of each platelet?
31. Hybrid functional Petri net of platelet activation TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc
32. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
33. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
34. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
35. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
36. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
37. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
38. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
39. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
40. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
41. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
42. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
43. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
44. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc Hybrid functional Petri net of platelet activation
45. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc
46. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc
47. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc
48. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA
49. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA
50. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA COX1
51. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA COX1
52. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA TXA2int COX1
53. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA TXA2int COX1
54. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA TXA2ext TXA2int COX1
55. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA TXA2ext TXA2int COX1
56. TXA2ext TP receptors PLC PIP2 PIP3 IP3R calcium receptor Ca2+ in cytozole PLA2 PL AA COX-1 PGH2 TXA2int TR1 TR2 TR3 TR4 TR5 TR6 TR7 TR8 TR9 TR10 Aspirin PGTF continuous place continuous transition normal arc test arc inhibitory arc AA TXA2ext TXA2int ASA COX1
57. COX1 AA TXA2int TR1 TR2 TXA2ext TR4 COX1inact TR3 ASA acytCOX1 TR5
58. COX1 AA TXA2int TR1 TR2 TXA2ext TR4 COX1inact TR3 ASA acytCOX1 TR5 Model
59. COX1 AA TXA2int TR1 TR2 TXA2ext TR4 COX1inact TR3 ASA acytCOX1 TR5 Model
60. COX1 AA TXA2int TR1 TR2 TXA2ext TR4 COX1inact TR3 ASA acytCOX1 TR5 Model // Place(name, initial_concentration) NodePtr txa2_ext (new Place("TXA2_ext" NodePtr aa (new Place("AA" NodePtr cox1 (new Place("COX1" NodePtr txa2_int (new Place("TXA2_int" // Transition(name, substrate, product, NodePtr tr1 (new Transition("TR1", tr1_e NodePtr tr2 (new Transition("TR2", tr2_e NodePtr tr3 (new Transition("TR3", tr3_e DSL D O M A I N - S P E C I F I C LANGUAGE
61. Visualisation
62. Visualisation +
63. Visualisation interactive +
64. Visualisation interactive +tweakable
65. Visualisation interactive +tweakable
66. Demo
67. EMITTED TXA2 ~20 cells WOUND VESSEL WALL TUNA model
68. WOUND VESSEL WALL New model EMITTED TXA2
69. WOUND VESSEL WALL New model EMITTED TXA2
70. WOUND VESSEL WALL New model EMITTED TXA2
71. WOUND VESSEL WALL New model AMPLIFIED ACTIVATION EMITTED TXA2
72. ~5 cells WOUND VESSEL WALL New model AMPLIFIED ACTIVATION EMITTED TXA2
73. Future work
74. Future work Applications
75. Improvements
76. Improvements: Physics Realistic uid dynamics model for the blood ow.
77. Improvements: DSL Editor Epsilon editor for easy pathway creation and integration.
78. { } MODELLING SIMULATION VISUALISATION
79. CrISp CENTRE FOR RESEARCH IN SYSTEMS PATHOLOGY { } MODELLING SIMULATION VISUALISATION
80. CrISp CENTRE FOR RESEARCH IN SYSTEMS PATHOLOGY { } MODELLING SIMULATION VISUALISATION DR UG T EST ING, PHARMACOKINE TICS, PHARMACODYNAMI CS, DRUG D IS TRI BUT ION, DRUG INTER AC TION
81. Thank you! Special thanks to Supervisor Dr Adam Sampson Prof James Bown GREGORY@GOLTSOV.INFO WWW.GREGORY.GOLTSOV.INFO