sbiosobol

Perform global sensitivity analysis by computing first- and total-order Sobol indices (requires Statistics and Machine Learning Toolbox)

Syntax

sobolResults = sbiosobol(modelObj,params,observables)

sobolResults = sbiosobol(modelObj,scenarios,observables)

sobolResults = sbiosobol(modelObj,params,observables,Name,Value)

Description

sobolResults = sbiosobol(modelObj,params,observables) performs global sensitivity analysis [1] on a SimBiology model modelObj by decomposing the variances of observables with respect to the sensitivity inputs params.

sobolResults = sbiosobol(modelObj,scenarios,observables) uses samples from scenarios, a SimBiology.Scenarios object, to perform the analysis.

sobolResults = sbiosobol(modelObj,params,observables,Name,Value) uses additional options specified by one or more name-value pair arguments.

Examples

Perform Global Sensitivity Analysis by Computing First- and Total-Order Sobol Indices

Load the tumor growth model.

sbioloadproject tumor_growth_vpop_sa.sbproj

Get a variant with the estimated parameters and the dose to apply to the model.

v = getvariant(m1);
d = getdose(m1,'interval_dose');

Get the active configset and set the tumor weight as the response.

cs = getconfigset(m1);
cs.RuntimeOptions.StatesToLog = 'tumor_weight';

Simulate the model and plot the tumor growth profile.

sbioplot(sbiosimulate(m1,cs,v,d));

Perform global sensitivity analysis (GSA) on the model to find the model parameters that the tumor growth is sensitive to.

First, retrieve model parameters of interest that are involved in the pharmacodynamics of the tumor growth. Define the model response as the tumor weight.

modelParamNames = {'L0','L1','w0','k1','k2'};
outputName = 'tumor_weight';

Then perform GSA by computing the first- and total-order Sobol indices using sbiosobol. Set 'ShowWaitBar' to true to show the simulation progress. By default, the function uses 1000 parameter samples to compute the Sobol indices [1].

rng('default');
sobolResults = sbiosobol(m1,modelParamNames,outputName,Variants=v,Doses=d,ShowWaitBar=true)

sobolResults = 
  Sobol with properties:

                Time: [444×1 double]
        SobolIndices: [5×1 struct]
            Variance: [444×1 table]
    ParameterSamples: [1000×5 table]
         Observables: {'[Tumor Growth].tumor_weight'}
      SimulationInfo: [1×1 struct]

You can change the number of samples by specifying the 'NumberSamples' name-value pair argument. The function requires a total of (number of input parameters + 2) * NumberSamples model simulations.

Show the mean model response, the simulation results, and a shaded region covering 90% of the simulation results.

plotData(sobolResults,ShowMedian=true,ShowMean=false);

You can adjust the quantile region to a different percentage by specifying 'Alphas' for the lower and upper quantiles of all model responses. For instance, an alpha value of 0.1 plots a shaded region between the 100 * alpha and 100 * (1 - alpha) quantiles of all simulated model responses.

plotData(sobolResults,Alphas=0.1,ShowMedian=true,ShowMean=false);

Plot the time course of the first- and total-order Sobol indices.

h = plot(sobolResults);
% Resize the figure.
h.Position(:) = [100 100 1280 800];

The first-order Sobol index of an input parameter gives the fraction of the overall response variance that can be attributed to variations in the input parameter alone. The total-order index gives the fraction of the overall response variance that can be attributed to any joint parameter variations that include variations of the input parameter.

From the Sobol indices plots, parameters L1 and w0 seem to be the most sensitive parameters to the tumor weight before the dose was applied at t = 7. But after the dose is applied, k1 and k2 become more sensitive parameters and contribute most to the after-dosing stage of the tumor weight. The total variance plot also shows a larger variance for the after-dose stage at t > 35 than for the before-dose stage of the tumor growth, indicating that k1 and k2 might be more important parameters to investigate further. The fraction of unexplained variance shows some variance at around t = 33, but the total variance plot shows little variance at t = 33, meaning the unexplained variance could be insignificant. The fraction of unexplained variance is calculated as 1 - (sum of all the first-order Sobol indices), and the total variance is calculated using var(response), where response is the model response at every time point.

You can also display the magnitudes of the sensitivities in a bar plot. Darker colors mean that those values occur more often over the whole time course.

bar(sobolResults);

You can specify more samples to increase the accuracy of the Sobol indices, but the simulation can take longer to finish. Use addsamples to add more samples. For example, if you specify 1500 samples, the function performs 1500 * (2 + number of input parameters) simulations.

gsaMoreSamples = addsamples(gsaResults,1500)

The SimulationInfo property of the result object contains various information for computing the Sobol indices. For instance, the model simulation data (SimData) for each simulation using a set of parameter samples is stored in the SimData field of the property. This field is an array of SimData objects.

sobolResults.SimulationInfo.SimData

 
   SimBiology SimData Array : 1000-by-7
 
   Index:    Name:         ModelName:         DataCount: 
   1           -           Tumor Growth Model 1          
   2           -           Tumor Growth Model 1          
   3           -           Tumor Growth Model 1          
   ...                                                   
   7000        -           Tumor Growth Model 1          
 

You can find out if any model simulation failed during the computation by checking the ValidSample field of SimulationInfo. In this example, the field shows no failed simulation runs.

all(sobolResults.SimulationInfo.ValidSample)

ans = 1×7 logical array

   1   1   1   1   1   1   1

SimulationInfo.ValidSample is a table of logical values. It has the same size as SimulationInfo.SimData. If ValidSample indicates that any simulations failed, you can get more information about those simulation runs and the samples used for those runs by extracting information from the corresponding column of SimulationInfo.SimData. Suppose that the fourth column contains one or more failed simulation runs. Get the simulation data and sample values used for that simulation using getSimulationResults.

[samplesUsed,sd,validruns] = getSimulationResults(sobolResults,4);

You can add custom expressions as observables and compute Sobol indices for the added observables. For example, you can compute the Sobol indices for the maximum tumor weight by defining a custom expression as follows.

% Suppress an information warning that is issued during simulation.
warnSettings = warning('off', 'SimBiology:sbservices:SB_DIMANALYSISNOTDONE_MATLABFCN_UCON');
% Add the observable expression.
sobolObs = addobservable(sobolResults,'Maximum tumor_weight','max(tumor_weight)','Units','gram');

Plot the computed simulation results showing the 90% quantile region.

h2 = plotData(sobolObs,ShowMedian=true,ShowMean=false);
h2.Position(:) = [100 100 1280 800];

You can also remove the observable by specifying its name.

gsaNoObs = removeobservable(sobolObs,'Maximum tumor_weight');

Restore the warning settings.

warning(warnSettings);

Input Arguments

modelObj — SimBiology model

SimBiology model object

SimBiology model, specified as a SimBiology model object.

params — Names of model parameters, species, or compartments

character vector | string | string vector | cell array of character vectors

Names of model parameters, species, or compartments, specified as a character vector, string, string vector, or cell array of character vectors.

Example: ["k1","k2"]

Data Types: char | string | cell

observables — Model responses

character vector | string | string vector | cell array of character vectors

Model responses, specified as a character vector, string, string vector, or cell array of character vectors. Specify the names of species, parameters, compartments, or observables.

Example: ["tumor_growth"]

Data Types: char | string | cell

scenarios — Source for drawing samples

SimBiology.Scenarios object

Source for drawing samples, specified as a SimBiology.Scenarios object.

• You must combine entries of the object elementwise.

• Entries must be independent random variables. If there are multiple entries, they must be uncorrelated.

• SamplingMethod of any entry must not be copula.

Name-Value Arguments

Specify optional pairs of arguments as Name1=Value1,...,NameN=ValueN, where Name is the argument name and Value is the corresponding value. Name-value arguments must appear after other arguments, but the order of the pairs does not matter.

Before R2021a, use commas to separate each name and value, and enclose Name in quotes.

Example: sobolResults = sbiosobol(modelObj,params,observables,'ShowWaitbar',true) specifies to show a simulation progress bar.

Bounds — Parameter bounds

numeric matrix

Parameter bounds, specified as a numeric matrix with two columns. The first column contains the lower bounds and the second column contains the upper bounds. The number of rows must be equal to the number of parameters in params.

If a parameter has a nonzero value, the default bounds are ±10% of the value. If the parameter value is zero, the default bounds are [0 1].

Example: [0.5 5]

Data Types: double

Doses — Doses to use during simulations

ScheduleDose object | RepeatDose object | vector of dose objects

Doses to use during model simulations, specified as a ScheduleDose or RepeatDose object or a vector of dose objects.

Variants — Variants to apply before simulations

variant object | vector of variant objects

Variants to apply before model simulations, specified as a variant object or vector of variant objects.

When you specify multiple variants with duplicate specifications for a property's value, the last occurrence for the property value in the array of variants is used during simulation.

NumberSamples — Number of samples to compute Sobol indices

1000 (default) | positive integer

Number of samples to compute Sobol indices, specified as the comma-separated pair consisting of 'NumberSamples' and a positive integer. The function requires (number of input params + 2) * NumberSamples model simulations to compute the first- and total-order Sobol indices.

Data Types: double

Distributions — Probability distributions

prob.UniformDistribution (default) | prob.ProbabilityDistribution object | vector of prob.ProbabilityDistribution objects

Probability distributions used to draw samples, specified as a prob.ProbabilityDistribution object or vector of these objects. Specify a scalar prob.ProbabilityDistribution or vector of length N, where N is the number of input parameters. You can create distribution objects to sample from various distributions, such as uniform, normal, or lognormal distributions, using makedist (Statistics and Machine Learning Toolbox).

If you specify a scalar prob.ProbabilityDistribution object, and there are multiple input parameters, sbiosobol uses the same distribution object to draw samples for each parameter.

You cannot specify this argument together with Bounds.

You cannot specify this argument when a SimBiology.Scenarios object is an input.

SamplingMethod — Method to generate parameter samples

'Sobol' (default) | character vector | string

Method to generate parameter samples, specified as a character vector or string. Valid options are:

• 'Sobol' — Use the low-discrepancy Sobol sequence to generate samples.

• 'Halton' — Use the low-discrepancy Halton sequence to generate samples.

• 'lhs' — Use the low-discrepancy Latin hypercube samples.

• 'random' — Use uniformly distributed random samples.

Data Types: char | string

SamplingOptions — Options for sampling method

struct

Options for the sampling method, specified as a scalar struct. The options differ depending on the sampling method: sobol, halton, or lhs.

For sobol and halton, specify each field name and value of the structure according to each name-value argument of the sobolset (Statistics and Machine Learning Toolbox) or haltonset (Statistics and Machine Learning Toolbox) function. SimBiology uses the default value of 1 for the Skip argument for both methods. For all other name-value arguments, the software uses the same default values of sobolset or haltonset. For instance, set up a structure for the Leap and Skip options with nondefault values as follows.

s1.Leap = 50;
s1.Skip = 0;

For lhs, there are three samplers that support different sampling options.

• If you specify a covariance matrix, SimBiology uses lhsnorm (Statistics and Machine Learning Toolbox) for sampling. SamplingOptions argument is not allowed.

• Otherwise, use the field name UseLhsdesign to select a sampler.

  • If the value is true, SimBiology uses lhsdesign (Statistics and Machine Learning Toolbox). You can use the name-value arguments of lhsdesign to specify the field names and values.

  • If the value is false (default), SimBiology uses a nonconfigurable Latin hypercube sampler that is different from lhsdesign. This sampler does not require Statistics and Machine Learning Toolbox™. SamplingOptions cannot contain any other options, except UseLhsdesign.

For instance, set up a structure to use lhsdesign with the Criterion and Iterations options.

s2.UseLhsdesign  = true;
s2.Criterion     = "correlation";
s2.Iterations    = 10;

You cannot specify this argument when a SimBiology.Scenarios object is an input.

StopTime — Simulation stop time

nonnegative scalar

Simulation stop time, specified as a nonnegative scalar. If you specify neither StopTime nor OutputTimes, the function uses the stop time from the active configuration set of the model. You cannot specify both StopTime and OutputTimes.

Data Types: double

OutputTimes — Simulation output times

numeric vector

Simulation output times, specified as the comma-separated pair consisting of 'OutputTimes' and a numeric vector. The function computes the Sobol indices at these output time points. You cannot specify both StopTime and OutputTimes. By default, the function uses the output times of the first model simulation.

Example: [0 1 2 3.5 4 5 5.5]

Data Types: double

UseParallel — Flag to run model simulations in parallel

false (default) | true

Flag to run model simulations in parallel, specified as true or false. When the value is true and Parallel Computing Toolbox™ is available, the function runs simulations in parallel.

Data Types: logical

Accelerate — Flag to turn on model acceleration

true (default) | false

Flag to turn on model acceleration, specified as true or false.

Data Types: logical

InterpolationMethod — Method for interpolation of model simulations

"interp1q" (default) | character vector | string

Method for interpolation of model responses to a common set of output times, specified as a character vector or string. The valid options follow.

• "interp1q" — Use the interp1q function.

• Use the interp1 function by specifying one of the following methods:

  • "nearest"

  • "linear"

  • "spline"

  • "pchip"

  • "v5cubic"

• "zoh" — Specify zero-order hold.

Data Types: char | string

ShowWaitbar — Flag to show progress of model simulations

false (default) | true

Flag to show the progress of model simulations by displaying a progress bar, specified as the comma-separated pair consisting of 'ShowWaitbar' and true or false. By default, no wait bar is displayed.

Data Types: logical

Output Arguments

sobolResults — Results containing Sobol indices

SimBiology.gsa.Sobol object

Results containing the first- and total-order Sobol indices, returned as a SimBiology.gsa.Sobol object. The object also contains the parameter sample values and model simulation data used to compute the Sobol indices.

The results object can contain a significant amount of simulation data (SimData). The size of the object exceeds (1 + number of observables) * number of output time points * (2 + number of parameters) * number of samples * 8 bytes. For example, if you have one observable, 500 output time points, 8 parameters, and 100,000 samples, the object size is (1 + 1) * 500 * (2 + 8) * 100000 * 8 bytes = 8 GB. If you need to save such large objects, use this syntax:

save(fileName,variableName,'-v7.3');

For details, see MAT-file version.

More About

Saltelli Method to Compute Sobol Indices

sbiosobol implements the Saltelli method [1] to compute Sobol indices.

Consider a SimBiology model response Y expressed as a mathematical model $$Y=f\left(X_1,X_2,X_3,\mathrm{...},X_k\right)$$, where X_i is a model parameter and i = 1,…,k.

The first-order Sobol index (S_i) gives the fraction of the overall response variance V(Y) that can be attributed to variations in X_i alone. S_i is defined as follows.

$$S_i=\frac{V_{X_i}\left(E_{X_{\sim i}}\left(Y|X_i\right)\right)}{V\left(Y\right)}$$

The total-order Sobol index (S_Ti) gives the fraction of the overall response variance V(Y) that can be attributed to any joint parameter variations that include variations of X_i. S_Ti is defined as follows.

$$S_{Ti}=1-\frac{V_{X_{\sim i}}\left(E_{X_i}\left(Y|X_{\sim i}\right)\right)}{V\left(Y\right)}=\frac{E_{X_{\sim i}}\left(V_{X_i}\left(Y|X_{\sim i}\right)\right)}{V\left(Y\right)}$$

To compute individual values for Y corresponding to samples of parameters X₁, X₁, …, X_k, consider two independent sampling matrices A and B.

$$A=\left(\begin{array}{cccc}{X}_{11}& X_{12}& \mathrm{...}& X_{1k}\\ X_{21}& X_{22}& \mathrm{...}& X_{2k}\\ \mathrm{...}& \mathrm{...}& \mathrm{...}& \mathrm{...}\\ X_{n1}& X_{n2}& \mathrm{...}& X_{nk}\end{array}\right)$$

$$B=\left(\begin{array}{cccc}{X}_{11}^{\text{'}}& X_{12}^{\text{'}}& \mathrm{...}& X_{1k}^{\text{'}}\\ X_{21}^{\text{'}}& X_{22}^{\text{'}}& \mathrm{...}& X_{2k}^{\text{'}}\\ \mathrm{...}& \mathrm{...}& \mathrm{...}& \mathrm{...}\\ X_{n1}^{\text{'}}& X_{n2}^{\text{'}}& \mathrm{...}& X_{nk}^{\text{'}}\end{array}\right)$$

n is the sample size. Each row of the matrices A and B corresponds to one parameter sample set, which is a single realization of model parameter values.

Estimates for S_i and S_Ti are obtained from model simulation results using sample values from the matrices A, B, and $${{\displaystyle A}}_B^i$$, which is a matrix where all columns are from A except the ith column, which is from B for i = 1, 2, …, params.

$${{\displaystyle A}}_B^i=\left(\begin{array}{cccccc}{X}_{11}& X_{12}& \mathrm{...}& X_{1i}^{\text{'}}& \mathrm{...}& X_{1k}\\ X_{21}& X_{22}& \mathrm{...}& X_{2i}^{\text{'}}& \mathrm{...}& X_{2k}\\ \mathrm{...}& \mathrm{...}& \mathrm{...}& \mathrm{...}& \mathrm{...}& \mathrm{...}\\ X_{n1}& X_{n2}& \mathrm{...}& X_{ni}^{\text{'}}& \mathrm{...}& X_{nk}\end{array}\right)$$

The formulas to approximate the first- and total-order Sobol indices are as follows.

$${\widehat{S}}_i=\frac{\frac{1}{n}{\displaystyle \sum _{j=1}^{n}f{(B)}_j\left(f{\left({{\displaystyle A}}_B^i\right)}_j-f{(A)}_j\right)}}{V(Y)}$$

$${\widehat{S}}_{Ti}=\frac{\frac{1}{2n}{\displaystyle \sum _{j=1}^n{\left(f{(A)}_j-f{\left({{\displaystyle A}}_B^i\right)}_j\right)}^2}}{V(Y)}$$

f(A), f(B), and $$f{\left({{\displaystyle A}}_B^i\right)}_j$$ are the model simulation results using the parameter sample values from matrices A, B, and $${{\displaystyle A}}_B^i$$.

The matrix A corresponds to the ParameterSamples property of the Sobol results object (resultsObj.ParameterSamples). The matrix B corresponds to the SupportSamples property (resultsObj.SimulationInfo.SupportSamples).

The $${{\displaystyle A}}_B^i$$ matrices are stored in the SimData structure of the SimulationInfo property (resultsObj.SimulationInfo.SimData). The size of SimulationInfo.SimData is NumberSamples-by-params + 2, where NumberSamples is the number of samples and param is the number of input parameters. The number of columns is 2 + params because the first column of SimulationInfo.SimData contains the model simulation results using the sample matrix A. The second column contains simulation results using SupportSamples, which is another sample matrix B. The rest of the columns contain simulation results using $${{\displaystyle A}}_B^1$$, $${{\displaystyle A}}_B^2$$, …, $${{\displaystyle A}}_B^i$$, …, $${{\displaystyle A}}_B^{params}$$. See getSimulationResults to retrieve the model simulation results and samples for a specified ith index ($${{\displaystyle A}}_B^i$$) from the SimulationInfo.SimData array.

References

[1] Saltelli, Andrea, Paola Annoni, Ivano Azzini, Francesca Campolongo, Marco Ratto, and Stefano Tarantola. “Variance Based Sensitivity Analysis of Model Output. Design and Estimator for the Total Sensitivity Index.” Computer Physics Communications 181, no. 2 (February 2010): 259–70. https://doi.org/10.1016/j.cpc.2009.09.018.

Version History

Introduced in R2020a