(* 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 = { CIS[t], CISRNA[t], CISnRNA1[t], CISnRNA2[t], CISnRNA3[t], CISnRNA4[t], CISnRNA5[t], Epo[t], EpoRJAK2[t], EpoRJAK2\[LetterSpace]CIS[t], EpoRpJAK2[t], SHP1[t], SHP1Act[t], SOCS3[t], SOCS3RNA[t], SOCS3nRNA1[t], SOCS3nRNA2[t], SOCS3nRNA3[t], SOCS3nRNA4[t], SOCS3nRNA5[t], STAT5[t], npSTAT5[t], p12EpoRpJAK2[t], p1EpoRpJAK2[t], p2EpoRpJAK2[t], pSTAT5[t] }; initialValues = { CIS[0] == 0.0, CISRNA[0] == 0.0, CISnRNA1[0] == 0.0, CISnRNA2[0] == 0.0, CISnRNA3[0] == 0.0, CISnRNA4[0] == 0.0, CISnRNA5[0] == 0.0, Epo[0] == 1.24997*^-07, EpoRJAK2[0] == 3.97622, EpoRJAK2\[LetterSpace]CIS[0] == 0.0, EpoRpJAK2[0] == 0.0, SHP1[0] == 26.7251, SHP1Act[0] == 0.0, SOCS3[0] == 0.0, SOCS3RNA[0] == 0.0, SOCS3nRNA1[0] == 0.0, SOCS3nRNA2[0] == 0.0, SOCS3nRNA3[0] == 0.0, SOCS3nRNA4[0] == 0.0, SOCS3nRNA5[0] == 0.0, STAT5[0] == 79.7535, npSTAT5[0] == 0.0, p12EpoRpJAK2[0] == 0.0, p1EpoRpJAK2[0] == 0.0, p2EpoRpJAK2[0] == 0.0, pSTAT5[0] == 0.0 }; rates = { reaction\[LetterSpace]1, reaction\[LetterSpace]10, reaction\[LetterSpace]11, reaction\[LetterSpace]12, reaction\[LetterSpace]13, reaction\[LetterSpace]14, reaction\[LetterSpace]15, reaction\[LetterSpace]16, reaction\[LetterSpace]17, reaction\[LetterSpace]18, reaction\[LetterSpace]19, reaction\[LetterSpace]2, reaction\[LetterSpace]20, reaction\[LetterSpace]21, reaction\[LetterSpace]22, reaction\[LetterSpace]23, reaction\[LetterSpace]24, reaction\[LetterSpace]25, reaction\[LetterSpace]26, reaction\[LetterSpace]27, reaction\[LetterSpace]28, reaction\[LetterSpace]29, reaction\[LetterSpace]3, reaction\[LetterSpace]30, reaction\[LetterSpace]31, reaction\[LetterSpace]32, reaction\[LetterSpace]33, reaction\[LetterSpace]34, reaction\[LetterSpace]35, reaction\[LetterSpace]36, reaction\[LetterSpace]4, reaction\[LetterSpace]5, reaction\[LetterSpace]6, reaction\[LetterSpace]7, reaction\[LetterSpace]8, reaction\[LetterSpace]9 }; rateEquations = { reaction\[LetterSpace]1 -> (cyt*JAK2ActEpo*Epo[t]*EpoRJAK2[t])/(1 + (SOCS3Inh*SOCS3[t])/SOCS3Eqc), reaction\[LetterSpace]10 -> (cyt*EpoRCISRemove*EpoRJAK2\[LetterSpace]CIS[t]*(p12EpoRpJAK2[t] + p1EpoRpJAK2[t]))/init\[LetterSpace]EpoRJAK2, reaction\[LetterSpace]11 -> (cyt*SHP1ActEpoR*(EpoRpJAK2[t] + p12EpoRpJAK2[t] + p1EpoRpJAK2[t] + p2EpoRpJAK2[t])*SHP1[t])/init\[LetterSpace]EpoRJAK2, reaction\[LetterSpace]12 -> cyt*SHP1Dea*SHP1Act[t], reaction\[LetterSpace]13 -> (cyt*STAT5ActJAK2*(EpoRpJAK2[t] + p12EpoRpJAK2[t] + p1EpoRpJAK2[t] + p2EpoRpJAK2[t])*STAT5[t])/(init\[LetterSpace]EpoRJAK2*(1 + (SOCS3Inh*SOCS3[t])/SOCS3Eqc)), reaction\[LetterSpace]14 -> (cyt*STAT5ActEpoR*(p12EpoRpJAK2[t] + p1EpoRpJAK2[t])^2*STAT5[t])/(init\[LetterSpace]EpoRJAK2^2*(1 + (CISInh*CIS[t])/CISEqc)*(1 + (SOCS3Inh*SOCS3[t])/SOCS3Eqc)), reaction\[LetterSpace]15 -> cyt*STAT5Imp*pSTAT5[t], reaction\[LetterSpace]16 -> nuc*STAT5Exp*npSTAT5[t], reaction\[LetterSpace]17 -> -(((-1 + ActD)*CISRNAEqc*CISRNATurn*nuc*npSTAT5[t])/init\[LetterSpace]STAT5), reaction\[LetterSpace]18 -> CISRNADelay*nuc*CISnRNA1[t], reaction\[LetterSpace]19 -> CISRNADelay*nuc*CISnRNA2[t], reaction\[LetterSpace]2 -> (cyt*JAK2EpoRDeaSHP1*EpoRpJAK2[t]*SHP1Act[t])/init\[LetterSpace]SHP1, reaction\[LetterSpace]20 -> CISRNADelay*nuc*CISnRNA3[t], reaction\[LetterSpace]21 -> CISRNADelay*nuc*CISnRNA4[t], reaction\[LetterSpace]22 -> CISRNADelay*nuc*CISnRNA5[t], reaction\[LetterSpace]23 -> CISRNATurn*cyt*CISRNA[t], reaction\[LetterSpace]24 -> (CISEqc*CISTurn*cyt*CISRNA[t])/CISRNAEqc, reaction\[LetterSpace]25 -> CISTurn*cyt*CIS[t], reaction\[LetterSpace]26 -> CISEqc*CISEqcOE*CISoe*CISTurn, reaction\[LetterSpace]27 -> -(((-1 + ActD)*nuc*SOCS3RNAEqc*SOCS3RNATurn*npSTAT5[t])/init\[LetterSpace]STAT5), reaction\[LetterSpace]28 -> nuc*SOCS3RNADelay*SOCS3nRNA1[t], reaction\[LetterSpace]29 -> nuc*SOCS3RNADelay*SOCS3nRNA2[t], reaction\[LetterSpace]3 -> (cyt*EpoRActJAK2*EpoRpJAK2[t])/(1 + (SOCS3Inh*SOCS3[t])/SOCS3Eqc), reaction\[LetterSpace]30 -> nuc*SOCS3RNADelay*SOCS3nRNA3[t], reaction\[LetterSpace]31 -> nuc*SOCS3RNADelay*SOCS3nRNA4[t], reaction\[LetterSpace]32 -> nuc*SOCS3RNADelay*SOCS3nRNA5[t], reaction\[LetterSpace]33 -> cyt*SOCS3RNATurn*SOCS3RNA[t], reaction\[LetterSpace]34 -> (cyt*SOCS3Eqc*SOCS3Turn*SOCS3RNA[t])/SOCS3RNAEqc, reaction\[LetterSpace]35 -> cyt*SOCS3Turn*SOCS3[t], reaction\[LetterSpace]36 -> SOCS3Eqc*SOCS3EqcOE*SOCS3oe*SOCS3Turn, reaction\[LetterSpace]4 -> (3*cyt*EpoRActJAK2*EpoRpJAK2[t])/((1 + EpoRCISInh*EpoRJAK2\[LetterSpace]CIS[t])*(1 + (SOCS3Inh*SOCS3[t])/SOCS3Eqc)), reaction\[LetterSpace]5 -> (3*cyt*EpoRActJAK2*p1EpoRpJAK2[t])/((1 + EpoRCISInh*EpoRJAK2\[LetterSpace]CIS[t])*(1 + (SOCS3Inh*SOCS3[t])/SOCS3Eqc)), reaction\[LetterSpace]6 -> (cyt*EpoRActJAK2*p2EpoRpJAK2[t])/(1 + (SOCS3Inh*SOCS3[t])/SOCS3Eqc), reaction\[LetterSpace]7 -> (cyt*JAK2EpoRDeaSHP1*p1EpoRpJAK2[t]*SHP1Act[t])/init\[LetterSpace]SHP1, reaction\[LetterSpace]8 -> (cyt*JAK2EpoRDeaSHP1*p2EpoRpJAK2[t]*SHP1Act[t])/init\[LetterSpace]SHP1, reaction\[LetterSpace]9 -> (cyt*JAK2EpoRDeaSHP1*p12EpoRpJAK2[t]*SHP1Act[t])/init\[LetterSpace]SHP1 }; parameters = { ActD -> 0.0, CISEqc -> 432.871, CISEqcOE -> 0.530261, CISInh -> 784653000.0, CISRNADelay -> 0.144775, CISRNAEqc -> 1.0, CISRNATurn -> 1000.0, CISTurn -> 0.00839842, CISoe -> 0.0, EpoRActJAK2 -> 0.267308, EpoRCISInh -> 1000000.0, EpoRCISRemove -> 5.42932, JAK2ActEpo -> 633253.0, JAK2EpoRDeaSHP1 -> 142.722, SHP1ActEpoR -> 0.001, SHP1Dea -> 0.00816391, SOCS3Eqc -> 173.653, SOCS3EqcOE -> 0.679157, SOCS3Inh -> 10.408, SOCS3RNADelay -> 1.06465, SOCS3RNAEqc -> 1.0, SOCS3RNATurn -> 0.00830844, SOCS3Turn -> 10000.0, SOCS3oe -> 0.0, STAT5ActEpoR -> 38.9757, STAT5ActJAK2 -> 0.0780965, STAT5Exp -> 0.0745155, STAT5Imp -> 0.0268889, epo\[LetterSpace]level -> 1.24997*^-07, init\[LetterSpace]EpoRJAK2 -> 3.97622, init\[LetterSpace]SHP1 -> 26.7251, init\[LetterSpace]STAT5 -> 79.7535, cyt -> 0.4, nuc -> 0.275 }; assignments = { }; events = { }; speciesAnnotations = { }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "", "extent" -> ""} }; (* Time evolution *) odes = { CIS'[t] == 1.0*reaction\[LetterSpace]24 +1.0*reaction\[LetterSpace]26 -1.0*reaction\[LetterSpace]25, CISRNA'[t] == 1.0*reaction\[LetterSpace]22 -1.0*reaction\[LetterSpace]23, CISnRNA1'[t] == 1.0*reaction\[LetterSpace]17 -1.0*reaction\[LetterSpace]18, CISnRNA2'[t] == 1.0*reaction\[LetterSpace]18 -1.0*reaction\[LetterSpace]19, CISnRNA3'[t] == 1.0*reaction\[LetterSpace]19 -1.0*reaction\[LetterSpace]20, CISnRNA4'[t] == 1.0*reaction\[LetterSpace]20 -1.0*reaction\[LetterSpace]21, CISnRNA5'[t] == 1.0*reaction\[LetterSpace]21 -1.0*reaction\[LetterSpace]22, Epo'[t] == 0.0 , EpoRJAK2'[t] == 1.0*reaction\[LetterSpace]2 +1.0*reaction\[LetterSpace]7 +1.0*reaction\[LetterSpace]8 +1.0*reaction\[LetterSpace]9 -1.0*reaction\[LetterSpace]1, EpoRJAK2\[LetterSpace]CIS'[t] == -1.0*reaction\[LetterSpace]10, EpoRpJAK2'[t] == 1.0*reaction\[LetterSpace]1 -1.0*reaction\[LetterSpace]2 -1.0*reaction\[LetterSpace]3 -1.0*reaction\[LetterSpace]4, SHP1'[t] == 1.0*reaction\[LetterSpace]12 -1.0*reaction\[LetterSpace]11, SHP1Act'[t] == 1.0*reaction\[LetterSpace]11 -1.0*reaction\[LetterSpace]12, SOCS3'[t] == 1.0*reaction\[LetterSpace]34 +1.0*reaction\[LetterSpace]36 -1.0*reaction\[LetterSpace]35, SOCS3RNA'[t] == 1.0*reaction\[LetterSpace]32 -1.0*reaction\[LetterSpace]33, SOCS3nRNA1'[t] == 1.0*reaction\[LetterSpace]27 -1.0*reaction\[LetterSpace]28, SOCS3nRNA2'[t] == 1.0*reaction\[LetterSpace]28 -1.0*reaction\[LetterSpace]29, SOCS3nRNA3'[t] == 1.0*reaction\[LetterSpace]29 -1.0*reaction\[LetterSpace]30, SOCS3nRNA4'[t] == 1.0*reaction\[LetterSpace]30 -1.0*reaction\[LetterSpace]31, SOCS3nRNA5'[t] == 1.0*reaction\[LetterSpace]31 -1.0*reaction\[LetterSpace]32, STAT5'[t] == 1.0*reaction\[LetterSpace]16 -1.0*reaction\[LetterSpace]13 -1.0*reaction\[LetterSpace]14, npSTAT5'[t] == 1.0*reaction\[LetterSpace]15 -1.0*reaction\[LetterSpace]16, p12EpoRpJAK2'[t] == 1.0*reaction\[LetterSpace]5 +1.0*reaction\[LetterSpace]6 -1.0*reaction\[LetterSpace]9, p1EpoRpJAK2'[t] == 1.0*reaction\[LetterSpace]3 -1.0*reaction\[LetterSpace]5 -1.0*reaction\[LetterSpace]7, p2EpoRpJAK2'[t] == 1.0*reaction\[LetterSpace]4 -1.0*reaction\[LetterSpace]6 -1.0*reaction\[LetterSpace]8, pSTAT5'[t] == 1.0*reaction\[LetterSpace]13 +1.0*reaction\[LetterSpace]14 -1.0*reaction\[LetterSpace]15 }; 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]}]