Gene Drives' Mathematical Modeling



Héctor M. Sánchez C. & Sean L. Wu
[Press spacebar to move through the slides]


I. General Picture


0) Gene Drives?

1) GM Modeling: The Old Ways...

2) MGDrivE: Gene-Drive Simulation

3) MGDrivE + MoNeT: Genetic Landscape Analysis

0) Gene Drives?



					
					
"Fighting malaria with genetic engineering | Valentino Gantz"
					"Genetic Engineering and Diseases – Gene Drive & Malaria"
					

				

				

					0) Gene Drives?
Omar Akbari, Anthony James, Ethan Bier, Valentino Gantz



					
					
"The Gene Drive Dilemma: We Can Alter Entire Species, but Should We?"
					

				

        

					1) GM Modeling: The Old Ways...
Héctor M. Sánchez C., John M Marshall



					
					
"Overcoming evolved resistance to population-suppressing homing-based gene drives"
					

				

				

					2) MGDrivE: Gene Drive Simulations
Héctor M. Sánchez C., Jared B. Bennett, Sean L. Wu, John M Marshall



					

                    "MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations"

					

				

                

					2) MGDrivE: Gene Drive Simulations
Héctor M. Sánchez C., Jared B. Bennett, Sean L. Wu, John M Marshall



					

                    "MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations"

					

				

				

					3) MGDrivE + MoNeT: Genetic Landscape Analysis
Héctor M. Sánchez C., Víctor Ferman*, Gillian Chu, Maya Shen, Yunwen Ji, Sarafina Smith*, Biyonka Liang*, David L. Smith, John M. Marshall



					

					

				

                

					3) MGDrivE + MoNeT: Genetic Landscape Analysis
 Tomás León, Héctor M. Sánchez C., John M. Marshall



					

                    "São Tomé Movement Kernels"

					

				

			

			
			
			

				

					

						
II. Supression VS Replacement


                        
0) The Battle

						
1) Supression

						
2) Replacement

                        
3) Other

                        
4) Bottom Line

					

				

                

					0) The Battle



					

                    "MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations"

					

				

                

					1) Supression (No Resistance)



					

                    "Homing with No Resistance"

					

				

                

					1) Supression (Resistance)



					

                    "Homing with Resistance"

					

				

                

					2) Replacement (Transient)



					

                    "Split Drive in Yorkeys Knob"

					

				

                

					2) Replacement (Threshold-Dependent)



					

                    "Confinement and reversibility of threshold-dependent gene drive systems in mosquito populations"

					

				

                

					3) Other



                    

                    "ERACR (Bakersfield)"

					


				

                

					4) Bottom-Line






                    There are a lot of gene-drive constructs and we need a flexible framework to test them in spatial and non-spatial settings.
					


				

			

			
			
			

				

					

						
III. Modeling Details


                        
1) MGDrivE v1

						
2) MGDrivE v2

                        
3) Other Modeling-Related Things...

					

				

				
                

					1.1) MGDrivE v1: Software Design
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


                    

                    "MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations"

					

				

				
				

						1.2) MGDrivE v1: Mathematical Model
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


						

						"MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations"

						

				

				
        

					2.1) MGDrivE v2: Stochastic Petri Net as Efficient Data Structure
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


					
						

					
					

				

				
				

					2.2) MGDrivE v2: Structural Properties
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


					
						

					
					

				

				
				

					2.3) MGDrivE v2: Sampling Algorithms 1
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


						

					

				

				
				

					2.4) MGDrivE v2: Sampling Algorithms 2
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


					
						

					
					

				

				
				

					2.5) MGDrivE v2: Time-inhomogeneous Hazards
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


					
						

					
					

				

				
				

					2.6) MGDrivE v2: Epidemiological Dynamics
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., Tomás León, John M. Marshall


					
						

					
					

				

				
				

					3.1) Survival Analysis as input to Stochastic Simulation
Sean L. Wu, Jared B. Bennett, Héctor M. Sánchez C., John M. Marshall


					
						

					
					

				

				
			

            
			
			

					

							
 Team, Papers, and Questions

							
								



										


                                        PIs: John Marshall, David L. Smith


										Postdocs: Héctor M. Sánchez C., Tomás León, Victor Ferman*


										PhD Students: Jared Bennett, Sean L. Wu


										Undergraduate Students: Gillian Chu, Maya Shen, Yunwen Ji, Biyonka Liang*, Sarafina Smith*, Sabrina Wong*
                                

                                
                                        "Confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations."

                                        "A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment."

                                        "Development of a confinable gene drive system in the human disease vector, Aedes aegypti."

                                        "Reply to 'Concerns about the feasibility of using “precision guided sterile males” to control insects'."

                                        "Transforming insect population control with precision guided sterile males with demonstration in flies."

                                        "MGDrivE: A modular simulation framework for the spread of gene drives through spatially‐explicit mosquito populations."

                                        "Consequences of resistance evolution in a Cas9-based sex-conversion suppression gene drive for insect pest management."

                                        "Overcoming evolved resistance to population-suppressing homing-based gene drives."