Create SPR_fitting.md

docs/pages.jl

@@ -22,8 +22,7 @@ pages = Any[
             "model_creation/examples/basic_CRN_library.md",
             "model_creation/examples/programmatic_generative_linear_pathway.md",
             "model_creation/examples/hodgkin_huxley_equation.md",
-            "model_creation/examples/smoluchowski_coagulation_equation.md"
-        ]
+            "model_creation/examples/smoluchowski_coagulation_equation.md"]
     ],
     "Model simulation and visualization" => Any[
         "model_simulation/simulation_introduction.md",
@@ -51,8 +50,8 @@ pages = Any[
         # "inverse_problems/structural_identifiability.md",
         "inverse_problems/global_sensitivity_analysis.md",
         "Examples" => Any[
-            "inverse_problems/examples/ode_fitting_oscillation.md"
-        ]
+            "inverse_problems/examples/ode_fitting_oscillation.md",
+            "inverse_problems/examples/SPR_fitting.md"]
     ],
     "Spatial modelling" => Any[
         "spatial_modelling/lattice_reaction_systems.md",
@@ -65,3 +64,4 @@ pages = Any[
     "API" => "api.md",
     "Developer Documentation" => "devdocs/dev_guide.md"
 ]
+

docs/src/inverse_problems/examples/SPR_fitting.md

@@ -0,0 +1,110 @@
+# [Surface Plasmon Resonance Model Example](@id surface_plasmon_resonance_model_Example)
+This tutorial shows how to programmatically construct a ['ReactionSystem'](@ref) corresponding to the chemistry underlying the [Surface Plasmon Resonance Model](https://en.wikipedia.org/wiki/Surface_plasmon_resonance) using [ModelingToolkit](http://docs.sciml.ai/ModelingToolkit/stable/)/[Catalyst](http://docs.sciml.ai/Catalyst/stable/). You can find a simpler constructruction of this model [here](https://docs.sciml.ai/Catalyst/stable/catalyst_applications/parameter_estimation/) in the example of parameter estimation. 
+
+Using the symbolic interface, we will create our states/species, define our reactions, and add a discrete event. This model is simulated and used to generate sample data points with added noise and then used to fit parameters in iterations. This event will correspond to the time at which the antibody stop binding to antigen and switch to dissociating. 
+
+We begin by importing some necessary packages. 
+```julia
+using ModelingToolkit, Catalyst
+using Optimization, OptimizatizationOptimJL
+using Plots
+```
+In this example, the concentration of antigen,`\beta` is varied to determine the constant of proportionality, `\alpha`, `k_{on}`(association rate constant), and `k_{off}` (dissociation rate constant) which characterized the binding interaction between the antigen and the immobilized receptor molecules on the sensor slide. We start by defining our reaction equations, parameters, variables, event, and states. 
+```julia
+osys = @reaction_network begin
+    @variables t 
+    @parameters k_on=100.0 k_off α
+    @species A(t)B(t)
+
+    @discrete_events begin
+        t == switch_time => [k_on ~ 0.0] 
+    end
+
+    α*k_on, A --> B
+    k_off, B --> A
+end
+
+switch_time = 2.0
+
+tspan = (0.0, 4.0)
+alpha_list = [0.1, 0.2, 0.3, 0.4] #list of concentrations 
+```
+Iterating over values of `\alpha`, now we create a list of ODE solutions and set the initial conditions of our states and parameters. 
+```julia 
+results_list = []
+
+u0 = [:A => 10.0, :B => 0.0]
+p_real = [k_on => 100.0, k_off => 10.0, α => 1.0]
+oprob = ODEProblem(osys, u0, tspan, p_real)
+sample_times = range(tspan[1]; stop = tspan[2], length = 1001) 
+
+for alpha in alpha_list
+    p_real = [k_on => 100.0, k_off => 10.0, α => alpha]
+    oprobr = remake(oprob, p=p_real)
+    sol_real = solve(oprobr, Tsit5(); tstops = sample_times)
+
+    push!(results_list, sol_real(sample_times))
+end
+```
+```@example ceq3
+default(; lw = 3, framestyle = :box, size = (800, 400))
+p = plot()
+plot(p, sample_times, results_list[1][2,:])
+plot!(p, sample_times, results_list[2][2,:])
+plot!(p, sample_times, results_list[3][2,:])
+plot!(p, sample_times, results_list[4][2,:])
+
+sample_vals = []
+for result in results_list
+    sample_val = Array(result)
+    sample_val .*= (1 .+ .1 * rand(Float64, size(sample_val)) .- .01)
+    push!(sample_vals, sample_val)
+end
+
+for val in sample_vals
+    scatter!(p, sample_times, val[2,:]; color = [:blue :red], legend = nothing)
+end
+plot(p)
+```
+Next, we create a function to fit the parameters. Here we are using `NelderMead()`. In order to achieve a better fit, we are incorporating all of our solutions into the loss function. We will fit seperately the association and dissociation signals so for the first estimate, `tend < switch_time`. 
+```julia 
+function optimise_p(pinit, tend)
+    function loss(p, _)
+        newtimes = filter(<=(tend), sample_times)
+        solutions = []
+        for alpha in alpha_list
+            newprob = remake(oprob; tspan = (0.0, tend), p = [k_on => p[1],k_off => p[2],α => alpha])
+            sol = Array(solve(newprob, Tsit5(); saveat = newtimes, tstops = switch_time))
+            push!(solutions,sol[2,:])
+        end
+        loss = 0
+        for (idx, solution) in enumerate(solutions)
+            loss += sum(abs2, p[3]*solution .- sample_vals[idx][2, 1:size(sol,2)])
+        end
+
+        return loss
+    end
+
+    optf = OptimizationFunction(loss)
+
+    optprob = OptimizationProblem(optf, pinit)
+    sol = solve(optprob, Optim.NelderMead())
+
+    return sol.u
+end
+
+p_estimate = optimise_p([100.0, 10.0, 1.0], 1.5)
+```
+Finally, we remake the solution using the estimate, fit the entire time span for some `alpha`, and plot the solution. 
+```julia
+alpha = 0.2
+newprob = remake(oprob; tspan = (0.0, 4.0), p = [k_on => p_estimate[1], k_off => p_estimate[2], α => alpha])
+newsol = solve(newprob, Tsit5(); tstops = switch_time)
+
+#plotting simulated sample date with new solution
+default(; lw = 3, framestyle = :box, size = (800, 400))
+
+scatter!(sample_times, sample_vals; color = [:darkblue :darkred], legend = nothing)
+
+plot!(newsol[2,:]; legend = nothing, color = [:blue :red], linestyle = :dash, tspan= (0.0, 4.0))
+```