int doit(int argc, char *argv[])
{
double i, j ;
cvodeSettings_t *settings = CvodeSettings_create();
variableIndex_t *speciesVI, *parameterVI, *parameter2VI;
integratorInstance_t *integratorInstance;
char *modelStr, *parameterStr, *parameter2Str, *speciesStr;
double parameter, parameterEnd, parameterStepSize,
parameter2, parameter2End, parameter2StepSize,
errorTolerance, relativeErrorTolerance, endtime, initCond, maxDiff, diff;
int maximumIntegrationSteps;
odeModel_t *model ;
if (argc < 11)
{
fprintf(
stderr,
"usage %s sbml-model variable parameter1 parameter1-start parameter1-end parameter1-step parameter2 parameter2-start parameter2-end parameter2-step [endtime] [error-tolerance] [relative-error-tolerance] [maximum integration steps]\n",
argv[0]);
exit(0);
}
modelStr = argv[1];
speciesStr = argv[2];
parameterStr = argv[3];
parameter = atof(argv[4]);
parameterEnd = atof(argv[5]);
parameterStepSize = atof(argv[6]);
parameter2Str = argv[7];
parameter2 = atof(argv[8]);
parameter2End = atof(argv[9]);
parameter2StepSize = atof(argv[10]);
if (argc > 12)
endtime = atof(argv[11]);
else
endtime = 10000;
if (argc > 13)
errorTolerance = atof(argv[12]);
else
errorTolerance = 1e-6;
if (argc > 14)
relativeErrorTolerance = atof(argv[13]);
else
relativeErrorTolerance = 1e-4;
if (argc > 15)
maximumIntegrationSteps = atoi(argv[14]);
else
maximumIntegrationSteps = 1e9;
model = ODEModel_createFromFile(modelStr);
RETURN_ON_ERRORS_WITH(1);
speciesVI = ODEModel_getVariableIndex(model, speciesStr);
parameterVI = ODEModel_getVariableIndex(model, parameterStr);
parameter2VI = ODEModel_getVariableIndex(model, parameter2Str);
RETURN_ON_ERRORS_WITH(1);
/* integrate until steady state */
if ( endtime == 0 )
{
/* stop integration upon a steady state */
CvodeSettings_setIndefinitely(settings, 1);
CvodeSettings_setSteadyStateThreshold(settings, 1e-9);
CvodeSettings_setHaltOnSteadyState(settings, 1);
CvodeSettings_setTime(settings, 1, 1);
}
else
{
CvodeSettings_setHaltOnSteadyState(settings, 0);
CvodeSettings_setIndefinitely(settings, 0);
CvodeSettings_setTime(settings, endtime, 1000);
}
/* absolute tolerance in Cvode integration */
CvodeSettings_setError(settings, errorTolerance);
/* relative tolerance in Cvode integration */
CvodeSettings_setRError(settings, relativeErrorTolerance);
/* maximum step number for CVode integration */
CvodeSettings_setMxstep(settings, maximumIntegrationSteps);
/* doesn't stop integration upon an event */
CvodeSettings_setHaltOnEvent(settings, 0);
/* don't Store time course history */
CvodeSettings_setStoreResults(settings, 0);
/* compile model */
CvodeSettings_setCompileFunctions(settings, 1);
integratorInstance = IntegratorInstance_create(model, settings);
printf("set xlabel '%s'\n", ODEModel_getVariableName(model, parameterVI));
printf("set ylabel '%s'\n", ODEModel_getVariableName(model, parameter2VI));
printf("splot '-' using 1:2:3 title '%s' with points pointtype 1 pointsize 1 palette\n",
ODEModel_getVariableName(model, speciesVI) );
/* remember initial condition of observed variable */
initCond = IntegratorInstance_getVariableValue(integratorInstance, speciesVI);
maxDiff = 0.0;
int error = 0 ;
int run = 0;
for ( run=0; run<2; run++ )
{
for (i = parameter; i <= parameterEnd; i += parameterStepSize)
{
for (j = parameter2; j <= parameter2End; j += parameter2StepSize)
{
/* add fourth parameter here */
IntegratorInstance_reset( integratorInstance);
RETURN_ON_ERRORS_WITH(1);
/* for the second run reset the initial condition of the
observed variable to a multiple of the maximum observed
difference of its value wrt to its initial condition */
if ( run == 1 )
IntegratorInstance_setVariableValue(integratorInstance,
speciesVI,
fabs(5*(initCond-maxDiff)));
IntegratorInstance_setVariableValue(integratorInstance,
parameterVI, i);
IntegratorInstance_setVariableValue(integratorInstance,
parameter2VI, j);
/* printf("ic %g\t", IntegratorInstance_getVariableValue(integratorInstance, speciesVI)); */
while(!IntegratorInstance_checkSteadyState(integratorInstance) &&
!IntegratorInstance_timeCourseCompleted(integratorInstance) )
{
IntegratorInstance_integrateOneStep(integratorInstance);
if (SolverError_getNum(ERROR_ERROR_TYPE) ||
SolverError_getNum(FATAL_ERROR_TYPE))
{
fprintf(stderr,
"ERROR at parameter 1 = %g, parameter 2 = %g\n", i, j);
DumpErrors();
error++;
}
}
/* printf("end %g\n", IntegratorInstance_getVariableValue(integratorInstance, speciesVI)); */
/* check whether the final value has largest difference to initial condition */
diff = fabs(initCond - IntegratorInstance_getVariableValue(integratorInstance, speciesVI));
if ( diff > maxDiff ) maxDiff = diff;
DumpState(integratorInstance, parameterVI, parameter2VI, speciesVI);
}
}
}
printf("end\n");
/* printf("end\n init %g, MAX DIFF %g, abs %g\n", initCond, maxDiff, fabs(initCond-maxDiff)); */
if ( error ) printf("\t%d errors occured\n", error);
IntegratorInstance_free(integratorInstance);
VariableIndex_free(parameterVI);
VariableIndex_free(parameter2VI);
VariableIndex_free(speciesVI);
ODEModel_free(model);
CvodeSettings_free(settings);
return 0;
}
int doit(void)
{
int i ;
double value;
cvodeSettings_t *settings ;
variableIndex_t *s1, *s2;
integratorInstance_t *integratorInstanceA;
integratorInstance_t *integratorInstanceB;
odeModel_t *model = ODEModel_createFromFile("basic-model1-forward-l2.xml");
RETURN_ON_ERRORS_WITH(1);
s1 = ODEModel_getVariableIndex(model, "S1");
s2 = ODEModel_getVariableIndex(model, "S2");
RETURN_ON_ERRORS_WITH(1);
/* Creating settings with default values */
settings = CvodeSettings_create();
/* Setting end time to .1, number of time steps to 1 and NULL
instead of an optional predefined time series (double *); due
to Indefinitely == 1, Printstep 1 will be ignored and Time =
0.1 will be used as timestep for infinite integration */
CvodeSettings_setTime(settings, .1, 1);
/* Setting Cvode Parameters: absolute and relative tolerances and
maximal internal step */
CvodeSettings_setErrors(settings, 1e-18, 1e-14, 500);
/* Setting Integration Switches: see documentation or
example simpleIntegratorInstance.c for details on
the passed values */
CvodeSettings_setSwitches(settings, 1, 1, 0, 0, 0, 0, 0);
/* use compiled model */
CvodeSettings_setCompileFunctions(settings, 0);
/* Generate two independent integrator instances from the same
odeModel and cvodeSettings */
integratorInstanceA = IntegratorInstance_create(model, settings);
RETURN_ON_ERRORS_WITH(1);
integratorInstanceB = IntegratorInstance_create(model, settings);
RETURN_ON_ERRORS_WITH(1);
DumpState(integratorInstanceA, integratorInstanceB, s1, s2);
for (i=0; i != 30; i++)
{
/* run integrations A and B */
IntegratorInstance_integrateOneStep(integratorInstanceA);
RETURN_ON_ERRORS_WITH(1);
IntegratorInstance_integrateOneStep(integratorInstanceB);
RETURN_ON_ERRORS_WITH(1);
/* While variable s1 from integration A is between 1e-15 and
1e-16, set variables s1 and s2 in integration B to some
value. This function also takes care of creating and
freeing CVODE solver structures when ODE variables are
changed!
*/
value = IntegratorInstance_getVariableValue(integratorInstanceA, s1);
if ( value < 1.e-15 && value > 1.e-16 )
{
IntegratorInstance_setVariableValue(integratorInstanceB,
s1,1.5e-15);
IntegratorInstance_setVariableValue(integratorInstanceB,
s2,1.5e-15);
}
DumpState(integratorInstanceA, integratorInstanceB, s1, s2);
}
IntegratorInstance_free(integratorInstanceA);
IntegratorInstance_free(integratorInstanceB);
VariableIndex_free(s1);
VariableIndex_free(s2);
ODEModel_free(model);
CvodeSettings_free(settings);
return 0;
}
int
main (int argc, char *argv[])
{
int i, j, k;
int neq, nsens;
odeModel_t *om;
odeSense_t *os;
cvodeSettings_t *set;
integratorInstance_t *ii;
variableIndex_t *p1, *p2, *p3, *vi;
double *weights;
/* Setting SBML ODE Solver integration parameters */
set = CvodeSettings_create();
CvodeSettings_setTime(set, 30, 10);
CvodeSettings_setErrors(set, 1e-15, 1e-10, 1e9);
CvodeSettings_setMethod(set, 0, 5);
/* CvodeSettings_setStoreResults(set, 0); */
CvodeSettings_setJacobian(set, 1); /* for testing only */
CvodeSettings_setCompileFunctions(set, 0); /* for testing only */
/* CvodeSettings_dump(set); */
CvodeSettings_setFIM(set); /* ACTIVATE FIM */
/* creating the odeModel */
om = ODEModel_createFromFile("MAPK.xml");
ii = IntegratorInstance_create(om, set);
printf("\nFirst try a few integrations without sensitivity\n");
IntegratorInstance_dumpNames(ii);
printf("\n");
for ( i=0; i<2; i++ )
{
printf("Run #%d:\n", i);
IntegratorInstance_integrate(ii);
/* IntegratorInstance_dumpData(ii); */
IntegratorInstance_printResults(ii, stderr);
IntegratorInstance_reset(ii);
printf("finished\n\n");
}
/* ACTIVATE SENSITIVITY ANALYSIS */
CvodeSettings_setSensitivity(set, 1);
/* 0: simultaneous 1: staggered, 2: staggered1
see CVODES user guide for details */
CvodeSettings_setSensMethod(set, 0);
/* reset integrator to new settings */
IntegratorInstance_reset(ii);
printf("Now Activate Sensitivity\n\n");
os = IntegratorInstance_getSensitivityModel(ii);
nsens = ODESense_getNsens(os);
printf("nsens = %i\n\n", nsens);
for ( i=0; i<nsens; i++ ) {
vi = ODESense_getSensParamIndexByNum(os, i);
printf("%s\n", ODEModel_getVariableName(om, vi) );
VariableIndex_free(vi);
}
printf("\n");
printf("sensitivities calculated for all constants\n");
p1 = ODESense_getSensParamIndexByNum(os, 1);
p2 = ODESense_getSensParamIndexByNum(os, 2);
p3 = ODESense_getSensParamIndexByNum(os, 3);
printf("sensitivities printed for constants %s, %s, %s\n\n",
ODEModel_getVariableName(om, p1),
ODEModel_getVariableName(om, p2),
ODEModel_getVariableName(om, p3));
/* create non-default weights for computation of FIM */
/* weights should be extracted from objective function! */
neq = ODEModel_getNeq(om);
ASSIGN_NEW_MEMORY_BLOCK(weights, neq, double, 0);
for ( i=0; i<neq; i++ )
weights[i] = 1.;
/* set weights (to non-default values) */
IntegratorInstance_setFIMweights(ii, weights, neq);
/* *** *** *** *** *** *** discrete data *** *** *** *** *** *** *** */
CvodeSettings_setDiscreteObservation(set);
printf("DISCRETE DATA\n\n");
i = 0;
while ( i < 2 )
{
printf("Run #%d:\n", i);
while( !IntegratorInstance_timeCourseCompleted(ii) )
{
IntegratorInstance_dumpPSensitivities(ii, p1);
IntegratorInstance_dumpPSensitivities(ii, p2);
IntegratorInstance_dumpPSensitivities(ii, p3);
if ( !IntegratorInstance_integrateOneStep(ii) )
break;
}
IntegratorInstance_dumpPSensitivities(ii, p1);
IntegratorInstance_dumpPSensitivities(ii, p2);
IntegratorInstance_dumpPSensitivities(ii, p3);
fprintf(stderr, "FIM =\n");
for ( j=0; j<nsens; j++ )
{
for ( k=0; k<nsens; k++ )
fprintf(stderr, "%g ", IntegratorInstance_getFIM(ii,j,k));
fprintf(stderr, "\n");
}
fprintf(stderr, "\n");
IntegratorInstance_reset(ii);
i++;
}
/* *** *** *** *** *** *** continuous data *** *** *** *** *** *** *** */
CvodeSettings_unsetDiscreteObservation(set);
printf("CONTINUOUS DATA\n\n");
i = 0;
while ( i < 2 )
{
printf("Run #%d:\n", i);
while( !IntegratorInstance_timeCourseCompleted(ii) )
{
IntegratorInstance_dumpPSensitivities(ii, p1);
IntegratorInstance_dumpPSensitivities(ii, p2);
IntegratorInstance_dumpPSensitivities(ii, p3);
if ( !IntegratorInstance_integrateOneStep(ii) )
break;
}
IntegratorInstance_dumpPSensitivities(ii, p1);
IntegratorInstance_dumpPSensitivities(ii, p2);
IntegratorInstance_dumpPSensitivities(ii, p3);
/* calculate FIM */
IntegratorInstance_CVODEQuad(ii);
fprintf(stderr, "FIM =\n");
for ( j=0; j<nsens; j++ )
{
for ( k=0; k<nsens; k++ )
fprintf(stderr, "%g ", IntegratorInstance_getFIM(ii,j,k));
fprintf(stderr, "\n");
}
fprintf(stderr, "\n");
IntegratorInstance_reset(ii);
i++;
}
fprintf(stderr, "finished\n");
/* VariableIndex_free(y); */
VariableIndex_free(p1);
VariableIndex_free(p2);
VariableIndex_free(p3);
free(weights);
/* now we have the results and can free the inputs */
IntegratorInstance_free(ii);
CvodeSettings_free(set);
ODEModel_free(om);
return (EXIT_SUCCESS);
}
