(* Generated by JWS Online *) (* This is an experimental feature of JWS Online. Please report any mistakes.*) (* Note that the following notable SBML entities or features are not supported in notebook outputyet: *) (* Events *) (* Constraints *) (* Units and UnitDefinitions *) (* AlgebraicRules *) (* conversionFactors *) variables = { ActivatedReceptorComplex[t], ActivatedReceptorComplexSTAT2c[t], ActivatedReceptorComplexSTAT2cSTAT1c[t], CP[t], IFN[t], IFNARdimer[t], IRF9c[t], IRF9n[t], ISGF3c[t], ISGF3cCP[t], ISGF3n[t], ISGF3nNP[t], JAK[t], NP[t], OccupiedISGF3nbindingsites[t], OccupiedISGF3nbindingsitesNP[t], OpenISGF3nbindingsites[t], PIAS[t], PIASISGF3n[t], ReceptorIFNAR1[t], ReceptorJAKcomplex[t], ReceptorTYKcomplex[t], SOCS1[t], STAT1c[t], STAT1cstarSTAT2cstar[t], STAT1cstarSTAT2cstarCP[t], STAT1n[t], STAT1nstarSTAT2nstar[t], STAT1nstarSTAT2nstarNP[t], STAT2c[t], STAT2cIRF9[t], STAT2n[t], STAT2nIRF9[t], TYK[t], mRNAc[t], mRNAn[t], preIFN[t], species6[t] }; initialValues = { ActivatedReceptorComplex[0] == 0.0, ActivatedReceptorComplexSTAT2c[0] == 0.0, ActivatedReceptorComplexSTAT2cSTAT1c[0] == 0.0, CP[0] == 20.0, IFN[0] == 0.0, IFNARdimer[0] == 0.0, IRF9c[0] == 45.0, IRF9n[0] == 0.0, ISGF3c[0] == 0.0, ISGF3cCP[0] == 0.0, ISGF3n[0] == 0.0, ISGF3nNP[0] == 0.0, JAK[0] == 26.0, NP[0] == 40.0, OccupiedISGF3nbindingsites[0] == 0.0, OccupiedISGF3nbindingsitesNP[0] == 0.0, OpenISGF3nbindingsites[0] == 500.0, PIAS[0] == 10.0, PIASISGF3n[0] == 0.0, ReceptorIFNAR1[0] == 1000.0, ReceptorJAKcomplex[0] == 0.0, ReceptorTYKcomplex[0] == 0.0, SOCS1[0] == 0.0, STAT1c[0] == 1500.0, STAT1cstarSTAT2cstar[0] == 0.0, STAT1cstarSTAT2cstarCP[0] == 0.0, STAT1n[0] == 0.0, STAT1nstarSTAT2nstar[0] == 0.0, STAT1nstarSTAT2nstarNP[0] == 0.0, STAT2c[0] == 250.0, STAT2cIRF9[0] == 0.0, STAT2n[0] == 250.0, STAT2nIRF9[0] == 0.0, TYK[0] == 13.0, mRNAc[0] == 0.0, mRNAn[0] == 0.0, preIFN[0] == 6.5, species6[0] == 1000.0 }; rates = { v\[LetterSpace]1, v\[LetterSpace]10, v\[LetterSpace]11, v\[LetterSpace]12, v\[LetterSpace]13, v\[LetterSpace]14, v\[LetterSpace]15, v\[LetterSpace]16, v\[LetterSpace]17, v\[LetterSpace]18, v\[LetterSpace]19, v\[LetterSpace]2, v\[LetterSpace]20, v\[LetterSpace]21, v\[LetterSpace]22, v\[LetterSpace]23, v\[LetterSpace]24, v\[LetterSpace]25, v\[LetterSpace]26, v\[LetterSpace]27, v\[LetterSpace]28, v\[LetterSpace]29, v\[LetterSpace]3, v\[LetterSpace]30, v\[LetterSpace]31, v\[LetterSpace]32, v\[LetterSpace]33, v\[LetterSpace]34, v\[LetterSpace]35, v\[LetterSpace]36, v\[LetterSpace]37, v\[LetterSpace]38, v\[LetterSpace]39, v\[LetterSpace]4, v\[LetterSpace]40, v\[LetterSpace]41, v\[LetterSpace]5, v\[LetterSpace]6, v\[LetterSpace]7, v\[LetterSpace]8, v\[LetterSpace]9 }; rateEquations = { v\[LetterSpace]1 -> cytoplasm*(-(k2*ReceptorTYKcomplex[t]) + k1*ReceptorIFNAR1[t]*TYK[t]), v\[LetterSpace]10 -> k19*ISGF3c[t] - k29*ISGF3n[t], v\[LetterSpace]11 -> PhosphoTransport*STAT1cstarSTAT2cstar[t] - k210*STAT1nstarSTAT2nstar[t], v\[LetterSpace]12 -> nucleus*(-(k211*ISGF3n[t]) + k111*IRF9n[t]*STAT1nstarSTAT2nstar[t]), v\[LetterSpace]13 -> nucleus*(-(k212*OccupiedISGF3nbindingsites[t]) + k112*ISGF3n[t]*OpenISGF3nbindingsites[t]), v\[LetterSpace]14 -> function4Transcription*nucleus, v\[LetterSpace]15 -> -(k214*mRNAc[t]) + k114*mRNAn[t], v\[LetterSpace]16 -> cytoplasm*function4, v\[LetterSpace]17 -> cytoplasm*function6, v\[LetterSpace]18 -> cytoplasm*function5, v\[LetterSpace]19 -> cytoplasm*k118*ActivatedReceptorComplex[t], v\[LetterSpace]2 -> cytoplasm*(-(k21*ReceptorJAKcomplex[t]) + k11*JAK[t]*species6[t]), v\[LetterSpace]20 -> IRF9deg*nucleus*IRF9n[t], v\[LetterSpace]21 -> cytoplasm*IRF9deg*STAT2cIRF9[t], v\[LetterSpace]22 -> IRF9deg*nucleus*STAT2nIRF9[t], v\[LetterSpace]23 -> cytoplasm*(k122*CP[t]*ISGF3c[t] - k222*ISGF3cCP[t]), v\[LetterSpace]24 -> cytoplasm*k123*ISGF3cCP[t], v\[LetterSpace]25 -> cytoplasm*(k124*CP[t]*STAT1cstarSTAT2cstar[t] - k224*STAT1cstarSTAT2cstarCP[t]), v\[LetterSpace]26 -> cytoplasm*k125*STAT1cstarSTAT2cstarCP[t], v\[LetterSpace]27 -> nucleus*(NPfreebinding*NP[t]*STAT1nstarSTAT2nstar[t] - NPfreeunbinding*STAT1nstarSTAT2nstarNP[t]), v\[LetterSpace]28 -> k127*nucleus*STAT1nstarSTAT2nstarNP[t], v\[LetterSpace]29 -> nucleus*(-(NPfreeunbinding*ISGF3nNP[t]) + NPfreebinding*ISGF3n[t]*NP[t]), v\[LetterSpace]3 -> cytoplasm*(-(k22*IFNARdimer[t]) + k12*IFN[t]*ReceptorJAKcomplex[t]*ReceptorTYKcomplex[t]), v\[LetterSpace]30 -> k129*nucleus*ISGF3nNP[t], v\[LetterSpace]31 -> nucleus*(k130*NP[t]*OccupiedISGF3nbindingsites[t] - k230*OccupiedISGF3nbindingsitesNP[t]), v\[LetterSpace]32 -> k131*nucleus*OccupiedISGF3nbindingsitesNP[t], v\[LetterSpace]33 -> nucleus*(k132*ISGF3n[t]*PIAS[t] - k232*PIASISGF3n[t]), v\[LetterSpace]34 -> cytoplasm*k133*mRNAc[t], v\[LetterSpace]35 -> -(k234*STAT1c[t]) + k134*STAT1n[t], v\[LetterSpace]36 -> -(k235*STAT2c[t]) + k135*STAT2n[t], v\[LetterSpace]37 -> cytoplasm*(k136*IRF9c[t]*STAT2c[t] - k236*STAT2cIRF9[t]), v\[LetterSpace]38 -> nucleus*(k137*IRF9n[t]*STAT2n[t] - k237*STAT2nIRF9[t]), v\[LetterSpace]39 -> k138*STAT2cIRF9[t] - k238*STAT2nIRF9[t], v\[LetterSpace]4 -> cytoplasm*k13*IFNARdimer[t], v\[LetterSpace]40 -> k139*IRF9c[t] - k239*IRF9n[t], v\[LetterSpace]41 -> cytoplasm*k140*preIFN[t], v\[LetterSpace]5 -> cytoplasm*statrecbinding*ActivatedReceptorComplex[t]*STAT2cIRF9[t], v\[LetterSpace]6 -> cytoplasm*(-(statrecunbinding*ActivatedReceptorComplexSTAT2c[t]) + statrecbinding*ActivatedReceptorComplex[t]*STAT2c[t]), v\[LetterSpace]7 -> cytoplasm*(-(statrecunbinding*ActivatedReceptorComplexSTAT2cSTAT1c[t]) + statrecbinding*ActivatedReceptorComplexSTAT2c[t]*STAT1c[t]), v\[LetterSpace]8 -> cytoplasm*k17*ActivatedReceptorComplexSTAT2cSTAT1c[t], v\[LetterSpace]9 -> cytoplasm*(-(k28*ISGF3c[t]) + k18*IRF9c[t]*STAT1cstarSTAT2cstar[t]) }; parameters = { IRF9deg -> 0.0001, NPfreebinding -> 0.01, NPfreeunbinding -> 0.1, PhosphoTransport -> 0.015, ReceptorSOCSdeg -> 1.2*^-05, Receptordegradation -> 0.0003, SOCSbinding -> 0.02, SOCSunbinding -> 0.1, STAT1Start -> 1500.0, STAT2Start -> 250.0, StartingJak -> 26.0, StartingReceptor -> 1000.0, StartingTyk -> 13.0, activatedsynth -> 0.045, constdeg -> 0.0005, cytoplasm -> 2.0, k1 -> 0.1, k11 -> 0.1, k111 -> 0.01, k112 -> 0.1, k113 -> 2.5*^-05, k114 -> 0.001, k118 -> 0.01, k12 -> 0.01, k122 -> 0.001, k123 -> 0.003, k124 -> 0.001, k125 -> 0.003, k127 -> 0.1, k129 -> 0.002, k13 -> 0.005, k130 -> 0.0001, k131 -> 0.1, k132 -> 0.1, k133 -> 0.0005, k134 -> 0.01, k135 -> 0.0014, k136 -> 0.01, k137 -> 0.01, k138 -> 0.00125, k139 -> 0.02, k140 -> 0.0009, k17 -> 8.0, k18 -> 0.1, k19 -> 0.015, k2 -> 0.05, k21 -> 0.05, k210 -> 0.0, k211 -> 0.01, k212 -> 0.1, k214 -> 0.0, k22 -> 0.01, k222 -> 0.2, k224 -> 0.2, k230 -> 0.1, k232 -> 0.1, k234 -> 0.00125, k235 -> 8.17*^-05, k236 -> 0.01, k237 -> 0.01, k238 -> 0.0014, k239 -> 0.005, k28 -> 0.1, k29 -> 0.0, nucleus -> 1.0, startkin -> 13.0, statrecbinding -> 0.002, statrecunbinding -> 4.0, vactivated -> 0.045, vconst -> 0.005, extVariable -> 0.0, default\[LetterSpace]compartment -> 1.0 }; assignments = { DNAbinding -> 2*OccupiedISGF3nbindingsites[t], function6 -> activatedsynth*mRNAc[t] - constdeg*SOCS1[t], function4Transcription -> k1*OccupiedISGF3nbindingsites[t], function5 -> Receptordegradation*ActivatedReceptorComplex[t] + ReceptorSOCSdeg*ActivatedReceptorComplex[t]*SOCS1[t], function4 -> vconst - IRF9deg*IRF9c[t] + vactivated*mRNAc[t] }; events = { }; speciesAnnotations = { }; reactionAnnotations = { }; units = { {"time" -> "min", "metabolite" -> "AU", "extent" -> "AU"} }; (* Time evolution *) odes = { ActivatedReceptorComplex'[t] == 0.5*v\[LetterSpace]4 +0.5*v\[LetterSpace]8 -0.5*v\[LetterSpace]6 -0.5*v\[LetterSpace]18 -0.5*v\[LetterSpace]5 -0.5*v\[LetterSpace]19, ActivatedReceptorComplexSTAT2c'[t] == 0.5*v\[LetterSpace]6 +0.5*v\[LetterSpace]5 -0.5*v\[LetterSpace]7, ActivatedReceptorComplexSTAT2cSTAT1c'[t] == 0.5*v\[LetterSpace]7 -0.5*v\[LetterSpace]8, CP'[t] == 0.5*v\[LetterSpace]26 +0.5*v\[LetterSpace]24 -0.5*v\[LetterSpace]23 -0.5*v\[LetterSpace]25, IFN'[t] == 0.5*v\[LetterSpace]41 -0.5*v\[LetterSpace]3, IFNARdimer'[t] == 0.5*v\[LetterSpace]3 +0.5*v\[LetterSpace]19 -0.5*v\[LetterSpace]4, IRF9c'[t] == 0.5*v\[LetterSpace]16 +0.5*v\[LetterSpace]24 +0.5*v\[LetterSpace]5 -0.5*v\[LetterSpace]37 -0.5*v\[LetterSpace]9 -0.5*v\[LetterSpace]40, IRF9n'[t] == 1.0*v\[LetterSpace]30 +1.0*v\[LetterSpace]32 +1.0*v\[LetterSpace]40 -1.0*v\[LetterSpace]12 -1.0*v\[LetterSpace]20 -1.0*v\[LetterSpace]38, ISGF3c'[t] == 0.5*v\[LetterSpace]9 -0.5*v\[LetterSpace]23 -0.5*v\[LetterSpace]10, ISGF3cCP'[t] == 0.5*v\[LetterSpace]23 -0.5*v\[LetterSpace]24, ISGF3n'[t] == 1.0*v\[LetterSpace]12 +1.0*v\[LetterSpace]10 -1.0*v\[LetterSpace]13 -1.0*v\[LetterSpace]33 -1.0*v\[LetterSpace]29, ISGF3nNP'[t] == 1.0*v\[LetterSpace]29 -1.0*v\[LetterSpace]30, JAK'[t] == 0.5*v\[LetterSpace]18 -0.5*v\[LetterSpace]2, NP'[t] == 1.0*v\[LetterSpace]28 +1.0*v\[LetterSpace]30 +1.0*v\[LetterSpace]32 -1.0*v\[LetterSpace]31 -1.0*v\[LetterSpace]29 -1.0*v\[LetterSpace]27, OccupiedISGF3nbindingsites'[t] == 1.0*v\[LetterSpace]13 -1.0*v\[LetterSpace]31, OccupiedISGF3nbindingsitesNP'[t] == 1.0*v\[LetterSpace]31 -1.0*v\[LetterSpace]32, OpenISGF3nbindingsites'[t] == 1.0*v\[LetterSpace]32 -1.0*v\[LetterSpace]13, PIAS'[t] == -1.0*v\[LetterSpace]33, PIASISGF3n'[t] == 1.0*v\[LetterSpace]33 , ReceptorIFNAR1'[t] == 0.5*v\[LetterSpace]18 -0.5*v\[LetterSpace]1, ReceptorJAKcomplex'[t] == 0.5*v\[LetterSpace]2 -0.5*v\[LetterSpace]3, ReceptorTYKcomplex'[t] == 0.5*v\[LetterSpace]1 -0.5*v\[LetterSpace]3, SOCS1'[t] == 0.5*v\[LetterSpace]17 , STAT1c'[t] == 0.5*v\[LetterSpace]26 +0.5*v\[LetterSpace]24 +0.5*v\[LetterSpace]35 -0.5*v\[LetterSpace]7, STAT1cstarSTAT2cstar'[t] == 0.5*v\[LetterSpace]8 -0.5*v\[LetterSpace]25 -0.5*v\[LetterSpace]11 -0.5*v\[LetterSpace]9, STAT1cstarSTAT2cstarCP'[t] == 0.5*v\[LetterSpace]25 -0.5*v\[LetterSpace]26, STAT1n'[t] == 1.0*v\[LetterSpace]28 +1.0*v\[LetterSpace]30 +1.0*v\[LetterSpace]32 -1.0*v\[LetterSpace]35, STAT1nstarSTAT2nstar'[t] == 1.0*v\[LetterSpace]11 -1.0*v\[LetterSpace]12 -1.0*v\[LetterSpace]27, STAT1nstarSTAT2nstarNP'[t] == 1.0*v\[LetterSpace]27 -1.0*v\[LetterSpace]28, STAT2c'[t] == 0.5*v\[LetterSpace]26 +0.5*v\[LetterSpace]24 +0.5*v\[LetterSpace]36 +0.5*v\[LetterSpace]21 -0.5*v\[LetterSpace]37 -0.5*v\[LetterSpace]6, STAT2cIRF9'[t] == 0.5*v\[LetterSpace]37 -0.5*v\[LetterSpace]39 -0.5*v\[LetterSpace]21 -0.5*v\[LetterSpace]5, STAT2n'[t] == 1.0*v\[LetterSpace]28 +1.0*v\[LetterSpace]22 +1.0*v\[LetterSpace]30 +1.0*v\[LetterSpace]32 -1.0*v\[LetterSpace]36 -1.0*v\[LetterSpace]38, STAT2nIRF9'[t] == 1.0*v\[LetterSpace]39 +1.0*v\[LetterSpace]38 -1.0*v\[LetterSpace]22, TYK'[t] == 0.5*v\[LetterSpace]18 -0.5*v\[LetterSpace]1, mRNAc'[t] == 0.5*v\[LetterSpace]15 -0.5*v\[LetterSpace]34, mRNAn'[t] == 1.0*v\[LetterSpace]14 -1.0*v\[LetterSpace]15, preIFN'[t] == -0.5*v\[LetterSpace]41, species6'[t] == 0.5*v\[LetterSpace]18 -0.5*v\[LetterSpace]2 }; timeCourse = NDSolve[Join[odes, initialValues]//.rateEquations//.assignments//.parameters, variables, {t, 0, 100}]; (* Steady-state solution initialized with result of time evolution *) findRootEquations = odes /.D[_[t],t]->0; findRootVariables = Partition[Flatten[{#, #/.timeCourse/.t->100} &/@variables],2]; steadyStateVariables = FindRoot[findRootEquations//.rateEquations//.assignments//.parameters, findRootVariables, MaxIterations->100] fluxes = #//.assignments//.parameters/.steadyStateVariables&/@rateEquations (* Plot the time evolution of the variables *) plotTable=Table[Plot[variables[[i]]/.parameters/.timeCourse,{t,0,100},PlotLegends->variables[[i]],PlotRange->Full],{i,Length[variables]}]