(* 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 = { Delay01\[LetterSpace]mSHP1[t], Delay02\[LetterSpace]mSHP1[t], Delay03\[LetterSpace]mSHP1[t], Delay04\[LetterSpace]mSHP1[t], Delay05\[LetterSpace]mSHP1[t], Delay06\[LetterSpace]mSHP1[t], Delay07\[LetterSpace]mSHP1[t], Delay08\[LetterSpace]mSHP1[t], ERK1[t], ERK2[t], Epo[t], EpoR[t], JAK2[t], MEK1[t], MEK2[t], Raf[t], SHP1[t], SOS[t], actSHP1[t], mSHP1[t], mSOS[t], pERK1[t], pERK2[t], pEpoR[t], pJAK2[t], pMEK1[t], pMEK2[t], pRaf[t], pSOS[t], ppERK1[t], ppERK2[t], ppMEK1[t], ppMEK2[t] }; initialValues = { Delay01\[LetterSpace]mSHP1[0] == 0.0, Delay02\[LetterSpace]mSHP1[0] == 0.0, Delay03\[LetterSpace]mSHP1[0] == 0.0, Delay04\[LetterSpace]mSHP1[0] == 0.0, Delay05\[LetterSpace]mSHP1[0] == 0.0, Delay06\[LetterSpace]mSHP1[0] == 0.0, Delay07\[LetterSpace]mSHP1[0] == 0.0, Delay08\[LetterSpace]mSHP1[0] == 0.0, ERK1[0] == 7.0, ERK2[0] == 21.0, Epo[0] == 50.0, EpoR[0] == 1.0, JAK2[0] == 2.0, MEK1[0] == 24.0, MEK2[0] == 11.0, Raf[0] == 3.7719, SHP1[0] == 10.7991, SOS[0] == 2.5101, actSHP1[0] == 0.0, mSHP1[0] == 0.0, mSOS[0] == 0.0, pERK1[0] == 0.0, pERK2[0] == 0.0, pEpoR[0] == 0.0, pJAK2[0] == 0.0, pMEK1[0] == 0.0, pMEK2[0] == 0.0, pRaf[0] == 0.0, pSOS[0] == 0.0, ppERK1[0] == 0.0, ppERK2[0] == 0.0, ppMEK1[0] == 0.0, ppMEK2[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]37, reaction\[LetterSpace]38, reaction\[LetterSpace]39, reaction\[LetterSpace]4, reaction\[LetterSpace]40, reaction\[LetterSpace]41, reaction\[LetterSpace]42, reaction\[LetterSpace]5, reaction\[LetterSpace]6, reaction\[LetterSpace]7, reaction\[LetterSpace]8, reaction\[LetterSpace]9 }; rateEquations = { reaction\[LetterSpace]1 -> cell*JAK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]Epo*Epo[t]*JAK2[t], reaction\[LetterSpace]10 -> cell*SHP1\[LetterSpace]delay*Delay06\[LetterSpace]mSHP1[t], reaction\[LetterSpace]11 -> cell*SHP1\[LetterSpace]delay*Delay07\[LetterSpace]mSHP1[t], reaction\[LetterSpace]12 -> cell*SHP1\[LetterSpace]delay*Delay08\[LetterSpace]mSHP1[t], reaction\[LetterSpace]13 -> actSHP1\[LetterSpace]deactivation*cell*actSHP1[t], reaction\[LetterSpace]14 -> cell*pEpoR\[LetterSpace]dephosphorylation\[LetterSpace]by\[LetterSpace]actSHP1*actSHP1[t]*pEpoR[t], reaction\[LetterSpace]15 -> cell*pJAK2\[LetterSpace]dephosphorylation\[LetterSpace]by\[LetterSpace]actSHP1*actSHP1[t]*pJAK2[t], reaction\[LetterSpace]16 -> cell*SOS\[LetterSpace]recruitment\[LetterSpace]by\[LetterSpace]pEpoR*pEpoR[t]*SOS[t], reaction\[LetterSpace]17 -> cell*mSOS\[LetterSpace]release\[LetterSpace]from\[LetterSpace]membrane*mSOS[t], reaction\[LetterSpace]18 -> cell*mSOS\[LetterSpace]induced\[LetterSpace]Raf\[LetterSpace]phosphorylation*mSOS[t]*Raf[t], reaction\[LetterSpace]19 -> cell*pRaf\[LetterSpace]dephosphorylation*pRaf[t], reaction\[LetterSpace]2 -> cell*EpoR\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pJAK2*EpoR[t]*pJAK2[t], reaction\[LetterSpace]20 -> cell*First\[LetterSpace]MEK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf*MEK2[t]*pRaf[t], reaction\[LetterSpace]21 -> cell*First\[LetterSpace]MEK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf*MEK1[t]*pRaf[t], reaction\[LetterSpace]22 -> cell*Second\[LetterSpace]MEK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf*pMEK2[t]*pRaf[t], reaction\[LetterSpace]23 -> cell*Second\[LetterSpace]MEK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf*pMEK1[t]*pRaf[t], reaction\[LetterSpace]24 -> cell*First\[LetterSpace]MEK\[LetterSpace]dephosphorylation*ppMEK2[t], reaction\[LetterSpace]25 -> cell*First\[LetterSpace]MEK\[LetterSpace]dephosphorylation*ppMEK1[t], reaction\[LetterSpace]26 -> cell*Second\[LetterSpace]MEK\[LetterSpace]dephosphorylation*pMEK2[t], reaction\[LetterSpace]27 -> cell*Second\[LetterSpace]MEK\[LetterSpace]dephosphorylation*pMEK1[t], reaction\[LetterSpace]28 -> cell*First\[LetterSpace]ERK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*ERK1[t]*ppMEK2[t], reaction\[LetterSpace]29 -> cell*First\[LetterSpace]ERK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*ERK2[t]*ppMEK2[t], reaction\[LetterSpace]3 -> cell*SHP1\[LetterSpace]activation\[LetterSpace]by\[LetterSpace]pEpoR*pEpoR[t]*SHP1[t], reaction\[LetterSpace]30 -> cell*First\[LetterSpace]ERK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*ERK1[t]*ppMEK1[t], reaction\[LetterSpace]31 -> cell*First\[LetterSpace]ERK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*ERK2[t]*ppMEK1[t], reaction\[LetterSpace]32 -> cell*Second\[LetterSpace]ERK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*pERK1[t]*ppMEK2[t], reaction\[LetterSpace]33 -> cell*Second\[LetterSpace]ERK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*pERK2[t]*ppMEK2[t], reaction\[LetterSpace]34 -> cell*Second\[LetterSpace]ERK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*pERK1[t]*ppMEK1[t], reaction\[LetterSpace]35 -> cell*Second\[LetterSpace]ERK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK*pERK2[t]*ppMEK1[t], reaction\[LetterSpace]36 -> cell*First\[LetterSpace]ERK\[LetterSpace]dephosphorylation*ppERK1[t], reaction\[LetterSpace]37 -> cell*First\[LetterSpace]ERK\[LetterSpace]dephosphorylation*ppERK2[t], reaction\[LetterSpace]38 -> cell*Second\[LetterSpace]ERK\[LetterSpace]dephosphorylation*pERK1[t], reaction\[LetterSpace]39 -> cell*Second\[LetterSpace]ERK\[LetterSpace]dephosphorylation*pERK2[t], reaction\[LetterSpace]4 -> cell*SHP1\[LetterSpace]delay*mSHP1[t], reaction\[LetterSpace]40 -> cell*ppERK\[LetterSpace]neg\[LetterSpace]feedback\[LetterSpace]on\[LetterSpace]mSOS*mSOS[t]*ppERK1[t], reaction\[LetterSpace]41 -> cell*ppERK\[LetterSpace]neg\[LetterSpace]feedback\[LetterSpace]on\[LetterSpace]mSOS*mSOS[t]*ppERK2[t], reaction\[LetterSpace]42 -> cell*pSOS\[LetterSpace]dephosphorylation*pSOS[t], reaction\[LetterSpace]5 -> cell*SHP1\[LetterSpace]delay*Delay01\[LetterSpace]mSHP1[t], reaction\[LetterSpace]6 -> cell*SHP1\[LetterSpace]delay*Delay02\[LetterSpace]mSHP1[t], reaction\[LetterSpace]7 -> cell*SHP1\[LetterSpace]delay*Delay03\[LetterSpace]mSHP1[t], reaction\[LetterSpace]8 -> cell*SHP1\[LetterSpace]delay*Delay04\[LetterSpace]mSHP1[t], reaction\[LetterSpace]9 -> cell*SHP1\[LetterSpace]delay*Delay05\[LetterSpace]mSHP1[t] }; parameters = { EpoR\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pJAK2 -> 3.15714, First\[LetterSpace]ERK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK -> 2.4927, First\[LetterSpace]ERK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK -> 2.44361, First\[LetterSpace]ERK\[LetterSpace]dephosphorylation -> 39.0886, First\[LetterSpace]MEK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf -> 0.687193, First\[LetterSpace]MEK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf -> 3.11919, First\[LetterSpace]MEK\[LetterSpace]dephosphorylation -> 0.130937, JAK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]Epo -> 0.0122149, SHP1\[LetterSpace]activation\[LetterSpace]by\[LetterSpace]pEpoR -> 0.408408, SHP1\[LetterSpace]delay -> 0.408408, SOS\[LetterSpace]recruitment\[LetterSpace]by\[LetterSpace]pEpoR -> 0.10271, Second\[LetterSpace]ERK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK -> 59.5251, Second\[LetterSpace]ERK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]ppMEK -> 53.0816, Second\[LetterSpace]ERK\[LetterSpace]dephosphorylation -> 3.00453, Second\[LetterSpace]MEK1\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf -> 667.957, Second\[LetterSpace]MEK2\[LetterSpace]phosphorylation\[LetterSpace]by\[LetterSpace]pRaf -> 215.158, Second\[LetterSpace]MEK\[LetterSpace]dephosphorylation -> 0.0732724, actSHP1\[LetterSpace]deactivation -> 0.0248773, mSOS\[LetterSpace]induced\[LetterSpace]Raf\[LetterSpace]phosphorylation -> 0.144515, mSOS\[LetterSpace]release\[LetterSpace]from\[LetterSpace]membrane -> 15.5956, pEpoR\[LetterSpace]dephosphorylation\[LetterSpace]by\[LetterSpace]actSHP1 -> 1.19995, pJAK2\[LetterSpace]dephosphorylation\[LetterSpace]by\[LetterSpace]actSHP1 -> 0.368384, pRaf\[LetterSpace]dephosphorylation -> 0.374228, pSOS\[LetterSpace]dephosphorylation -> 0.124944, ppERK\[LetterSpace]neg\[LetterSpace]feedback\[LetterSpace]on\[LetterSpace]mSOS -> 5122.68, scale\[LetterSpace]SOS -> 1.10228, scale\[LetterSpace]pEpoR -> 0.493312, scale\[LetterSpace]pJAK2 -> 0.21008, scale\[LetterSpace]ppERK -> 13.5981, scale\[LetterSpace]ppMEK -> 40.5364, cell -> 1.0 }; assignments = { rescaled\[LetterSpace]SOS -> scale\[LetterSpace]SOS*SOS[t], rescaled\[LetterSpace]pSOS -> scale\[LetterSpace]SOS*pSOS[t], rescaled\[LetterSpace]mSOS -> scale\[LetterSpace]SOS*mSOS[t], rescaled\[LetterSpace]ppMEK2 -> scale\[LetterSpace]ppMEK*ppMEK2[t], rescaled\[LetterSpace]ppMEK1 -> scale\[LetterSpace]ppMEK*ppMEK1[t], rescaled\[LetterSpace]ppERK2 -> scale\[LetterSpace]ppERK*ppERK2[t], rescaled\[LetterSpace]ppERK1 -> scale\[LetterSpace]ppERK*ppERK1[t], rescaled\[LetterSpace]pJAK2 -> scale\[LetterSpace]pJAK2*pJAK2[t], rescaled\[LetterSpace]pEpoR -> scale\[LetterSpace]pEpoR*pEpoR[t] }; events = { }; speciesAnnotations = { }; reactionAnnotations = { reaction\[LetterSpace]40->"http://identifiers.org/go/GO:0004707", reaction\[LetterSpace]40->"http://identifiers.org/ec-code/2.7.11.24", reaction\[LetterSpace]40->"http://identifiers.org/go/GO:0006468", reaction\[LetterSpace]40->"http://identifiers.org/reactome/REACT\[LetterSpace]1420.5", reaction\[LetterSpace]41->"http://identifiers.org/go/GO:0004707", reaction\[LetterSpace]41->"http://identifiers.org/ec-code/2.7.11.24", reaction\[LetterSpace]41->"http://identifiers.org/go/GO:0006468", reaction\[LetterSpace]41->"http://identifiers.org/reactome/REACT\[LetterSpace]1420.5" }; units = { {"time" -> "", "metabolite" -> "", "extent" -> ""} }; (* Time evolution *) odes = { Delay01\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]4 -1.0*reaction\[LetterSpace]5, Delay02\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]5 -1.0*reaction\[LetterSpace]6, Delay03\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]6 -1.0*reaction\[LetterSpace]7, Delay04\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]7 -1.0*reaction\[LetterSpace]8, Delay05\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]8 -1.0*reaction\[LetterSpace]9, Delay06\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]9 -1.0*reaction\[LetterSpace]10, Delay07\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]10 -1.0*reaction\[LetterSpace]11, Delay08\[LetterSpace]mSHP1'[t] == 1.0*reaction\[LetterSpace]11 -1.0*reaction\[LetterSpace]12, ERK1'[t] == 1.0*reaction\[LetterSpace]38 -1.0*reaction\[LetterSpace]28 -1.0*reaction\[LetterSpace]30, ERK2'[t] == 1.0*reaction\[LetterSpace]39 -1.0*reaction\[LetterSpace]29 -1.0*reaction\[LetterSpace]31, Epo'[t] == 0.0 , EpoR'[t] == 1.0*reaction\[LetterSpace]14 -1.0*reaction\[LetterSpace]2, JAK2'[t] == 1.0*reaction\[LetterSpace]15 -1.0*reaction\[LetterSpace]1, MEK1'[t] == 1.0*reaction\[LetterSpace]27 -1.0*reaction\[LetterSpace]21, MEK2'[t] == 1.0*reaction\[LetterSpace]26 -1.0*reaction\[LetterSpace]20, Raf'[t] == 1.0*reaction\[LetterSpace]19 -1.0*reaction\[LetterSpace]18, SHP1'[t] == 1.0*reaction\[LetterSpace]13 -1.0*reaction\[LetterSpace]3, SOS'[t] == 1.0*reaction\[LetterSpace]17 +1.0*reaction\[LetterSpace]42 -1.0*reaction\[LetterSpace]16, actSHP1'[t] == 1.0*reaction\[LetterSpace]12 -1.0*reaction\[LetterSpace]13, mSHP1'[t] == 1.0*reaction\[LetterSpace]3 -1.0*reaction\[LetterSpace]4, mSOS'[t] == 1.0*reaction\[LetterSpace]16 -1.0*reaction\[LetterSpace]17 -1.0*reaction\[LetterSpace]40 -1.0*reaction\[LetterSpace]41, pERK1'[t] == 1.0*reaction\[LetterSpace]28 +1.0*reaction\[LetterSpace]30 +1.0*reaction\[LetterSpace]36 -1.0*reaction\[LetterSpace]32 -1.0*reaction\[LetterSpace]34 -1.0*reaction\[LetterSpace]38, pERK2'[t] == 1.0*reaction\[LetterSpace]29 +1.0*reaction\[LetterSpace]31 +1.0*reaction\[LetterSpace]37 -1.0*reaction\[LetterSpace]33 -1.0*reaction\[LetterSpace]35 -1.0*reaction\[LetterSpace]39, pEpoR'[t] == 1.0*reaction\[LetterSpace]2 -1.0*reaction\[LetterSpace]14, pJAK2'[t] == 1.0*reaction\[LetterSpace]1 -1.0*reaction\[LetterSpace]15, pMEK1'[t] == 1.0*reaction\[LetterSpace]21 +1.0*reaction\[LetterSpace]25 -1.0*reaction\[LetterSpace]23 -1.0*reaction\[LetterSpace]27, pMEK2'[t] == 1.0*reaction\[LetterSpace]20 +1.0*reaction\[LetterSpace]24 -1.0*reaction\[LetterSpace]22 -1.0*reaction\[LetterSpace]26, pRaf'[t] == 1.0*reaction\[LetterSpace]18 -1.0*reaction\[LetterSpace]19, pSOS'[t] == 1.0*reaction\[LetterSpace]40 +1.0*reaction\[LetterSpace]41 -1.0*reaction\[LetterSpace]42, ppERK1'[t] == 1.0*reaction\[LetterSpace]32 +1.0*reaction\[LetterSpace]34 -1.0*reaction\[LetterSpace]36, ppERK2'[t] == 1.0*reaction\[LetterSpace]33 +1.0*reaction\[LetterSpace]35 -1.0*reaction\[LetterSpace]37, ppMEK1'[t] == 1.0*reaction\[LetterSpace]23 -1.0*reaction\[LetterSpace]25, ppMEK2'[t] == 1.0*reaction\[LetterSpace]22 -1.0*reaction\[LetterSpace]24 }; 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]}]