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| %% N803_shared_drug.m - solves model for 2 cohorts with shared drug pars | ||
| % | ||
| % /--------------------------------------------------------------\ | ||
| % | Date: 06/27/2022 | | ||
| % | Author: Jonathan Cody | | ||
| % | Affiliation: Purdue University | | ||
| % | Weldon School of Biomedical Engineering | | ||
| % | Pienaar Computational Systems Pharmacology Lab | | ||
| % \--------------------------------------------------------------/ | ||
| % | ||
| % Nomenclature: V = SIV virions [#/無] | ||
| % T8 = total CD8+ T cells [#/無] | ||
| % E0 = resting SIV-specific CD8+ T cells [#/無] | ||
| % Ea = active SIV-specific CD8+ T cells [#/無] | ||
| % B0 = resting bystander CD8+ T cells [#/無] | ||
| % Ba = active bystander CD8+ T cells [#/無] | ||
| % X = N803 at absorption site [pmol/kg] | ||
| % C = N803 plasma concentration [pM] | ||
| % R = regulation [] (dimensionless quantity) | ||
| % | ||
| %% ======================================================================== | ||
| % INPUTS | ||
| % ======================================================================== | ||
| % | ||
| % SoluTimes = ascending vector of days at which to evaluate solution | ||
| % | ||
| % DoseTimes = ascending vector of days at which to administer doses | ||
| % (elements of 'DoseTimes' must also be in 'SoluTimes') | ||
| % | ||
| % AllPars = vector of parameters (see list in function) | ||
| % | ||
| %% ======================================================================== | ||
| % OPTIONS | ||
| % ======================================================================== | ||
| % | ||
| % varargin = cell vector used to add optional inputs (see 'N803_model_2') | ||
| % | ||
| %% ======================================================================== | ||
| % OUTPUTS | ||
| % ======================================================================== | ||
| % | ||
| % Y_OUT(:,1) = V at points in 'SoluTimes' [log fold change] | ||
| % Y_OUT(:,2) = T8 at points in 'SoluTimes' [fold change] | ||
| % | ||
| % Pars = parameters for (including calculated) | ||
| % | ||
| %% ======================================================================== | ||
| % FUNCTION | ||
| % ======================================================================== | ||
| function [Y_OUT,Pars] = ... | ||
| N803_single(SoluTimes,DoseTimes,AllPars,varargin) | ||
|
|
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| % Rename inputed parameters ----------------------------------------------- | ||
| Vi = AllPars(01) ;% V initial value [log(#/mL)] | ||
| EBi = AllPars(02) ;% E+B initial value [#/無] | ||
| fE = AllPars(03) ;% initial frequency: E/(E+B) | ||
| fEA = AllPars(04) ;% initial frequency: Ea/E | ||
| q = AllPars(05) ;% V growth rate (if E+B were absent) [/d] | ||
| psi = AllPars(06) ;% Ba/Ea killing rate ratio [gB0/gE0] | ||
| V50E = AllPars(07) ;% 50% viral stimulation saturation for E [#/mL] | ||
| V50B = AllPars(08) ;% 50% viral stimulation saturation for B [#/mL] | ||
| mEn = AllPars(09) ;% normalized Ea reversion rate constant [] | ||
| mBn = AllPars(10) ;% normalized Ba reversion rate constant [] | ||
| EB50 = AllPars(11) ;% 50% E+B proliferation saturation [#/無] | ||
| pE = AllPars(12) ;% Ea proliferation rate constant [/d] | ||
| pB = AllPars(13) ;% Ba proliferation rate constant [/d] | ||
| d = AllPars(14) ;% E0/B0 death rate constant [/d] | ||
| dA = AllPars(15) ;% Ea/Ba death rate constant [/d] | ||
| Xi = AllPars(16) ;% X initial condition [pmol/kg] | ||
| ka = AllPars(17) ;% N803 absorption rate constant [/d] | ||
| ke = AllPars(18) ;% N803 elimination rate constant [/d] | ||
| vd = AllPars(19) ;% N803 'volume of distribution'/'bioavailability' [L/kg] | ||
| C50 = AllPars(20) ;% 50% N803 stimulation concentration [pM] (Cohort 1) | ||
| pm = AllPars(21) ;% E0/B0 maximum proliferation rate [] | ||
| aE1 = AllPars(22) ;% E activation stimulation factor [] | ||
| aB1 = AllPars(23) ;% B activation stimulation factor [] | ||
| sig = AllPars(24) ;% sB/sE regulation generation rate ratio [/d] | ||
| dR = AllPars(25) ;% R decay rate constant [/d] | ||
| gE2 = AllPars(26) ;% initial E killing regulation [] | ||
| gB2 = AllPars(27) ;% initial B killing regulation [] | ||
| p2 = AllPars(28) ;% initial E0/B0 proliferation regulation [] | ||
| aE2 = AllPars(29) ;% initial E activation regulation [] | ||
| aB2 = AllPars(30) ;% initial B activation regulation [] | ||
|
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| %% ------------------------------------------------------------------------ | ||
| % Calculate some initial conditions & parameters -------------------------- | ||
|
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||
| Vi = 10^(Vi-3) ;% V initial value [#/無] | ||
| V50E = V50E/1000 ;% 50% viral stimulation saturation for E [#/無] | ||
| V50B = V50B/1000 ;% 50% viral stimulation saturation for B [#/無] | ||
|
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||
| % restrict mE and mB such that initial activation aE and aB are positive | ||
| UE = (2*pE/(pE+dA))^7 ; | ||
| UB = 2*pB/(pB+dA) ; | ||
| mE = mEn*dA/(UE-1) ;% Ea reversion rate constant [/d] | ||
| mB = mBn*dA/(UB-1) ;% Ba reversion rate constant [/d] | ||
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| % solve for initial ratios below (based on active steady-state) | ||
| ZE = UE/(mE+dA) ; | ||
| for i = 1:7 | ||
| ZE = ZE + (2*pE)^(i-1)/(pE+dA)^i ;% EAi/aEi/E0i | ||
| end | ||
| ZB = 1/(pB+dA) + UB/(mB+dA) ;% BAi/aBi/B0i | ||
|
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| WE = 1 ; | ||
| for i = 1:7 | ||
| WE = WE + (mE+dA)*(pE+dA)^(i-1)/(2*pE)^i ;% EAi/E8i | ||
| end | ||
| WB = 1 + (mB+dA)/(2*pB) ;% BAi/B2i | ||
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| QE = mE/WE - 1/ZE ;% collection | ||
| QB = mB/WB - 1/ZB ;% collection | ||
|
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| fBA = 1/( 1 + QB/QE*(1-fEA)/fEA ) ;% initial frequency: Ba/B | ||
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| % solve for E and B initial conditions | ||
| Ei = EBi*fE ;% initial E | ||
| Bi = EBi*(1-fE) ;% initial B | ||
| EA = Ei*fEA ;% initial Ea | ||
| E0 = Ei*(1-fEA) ;% initial E0 | ||
| BA = Bi*fBA ;% initial Ea | ||
| B0 = Bi*(1-fBA) ;% initial E0 | ||
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| E = zeros(1,8) ;% initial E1-E8 | ||
| E(8) = EA/WE ;% E8 | ||
| E(7) = E(8) * (mE+dA)/(2*pE) ;% E7 | ||
| for i = 6:-1:1 | ||
| E(i) = E(i+1) * (pE+dA) / (2*pE) ;% E6 to E1 | ||
| end | ||
| B = BA/WB * [ (mB+dA) / (2*pB) , 1 ] ;% initial B1-B2 | ||
|
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| % solve for rate constants | ||
| aEi = E(1) / E0 * (pE+dA) ;% initial activation rate for E0 | ||
| aBi = B(1) / B0 * (pB+dA) ;% initial activation rate for B0 | ||
| aE0 = aEi * (V50E+Vi)/Vi * (1+aE2) ;% E0 activation rate constant [/d] | ||
| aB0 = aBi * (V50B+Vi)/Vi * (1+aB2) ;% B0 activation rate constant [/d] | ||
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| pi = d - QE*EA/E0 ;% initial proliferation rate for E0/B0 | ||
| p0 = pi * (EB50+EBi)/EB50 * (1+p2) ;% E0/B0 proliferation rate con [/d] | ||
| p1 = pm/p0 ;% E0/B0 proliferation stimulation factor | ||
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| gE0 = q / ( EA/(1+gE2) + psi*BA/(1+gB2) ) ;% Ea killing rate con [無/#-d] | ||
| gB0 = psi*gE0 ;% Ba killing rate constant [無/#-d] | ||
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| sE = dR / ( Vi/(V50E+Vi) + sig*Vi/(V50B+Vi) ) ;% regulation gen by E act | ||
| sB = sig*sE ;% regulation generation by B activation | ||
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| %% ------------------------------------------------------------------------ | ||
| % Prepare parameter and initial value vectors and call 'N803_model_2' ----- | ||
|
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| Pars(01) = q ;% V growth rate (if E+B were absent) [/d] | ||
| Pars(02) = gE0 ;% Ea killing rate constant [無/#-d] | ||
| Pars(03) = gB0 ;% Ba killing rate constant [無/#-d] | ||
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| Pars(04) = V50E ;% 50% viral stimulation saturation for E [#/無] | ||
| Pars(05) = V50B ;% 50% viral stimulation saturation for B [#/無] | ||
| Pars(06) = aE0 ;% E0 activation rate constant [/d] | ||
| Pars(07) = aB0 ;% B0 activation rate constant [/d] | ||
| Pars(08) = mE ;% Ea reversion rate constant [/d] | ||
| Pars(09) = mB ;% Ba reversion rate constant [/d] | ||
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| Pars(10) = EB50 ;% 50% E+B proliferation saturation [#/無] | ||
| Pars(11) = p0 ;% E0/B0 proliferation rate constant [/d] | ||
| Pars(12) = pE ;% Ea proliferation rate constant [/d] | ||
| Pars(13) = pB ;% Ba proliferation rate constant [/d] | ||
| Pars(14) = d ;% E0/B0 death rate constant [/d] | ||
| Pars(15) = dA ;% Ea/Ba death rate constant [/d] | ||
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| Pars(16) = Xi ;% X initial condition [pmol/kg] | ||
| Pars(17) = ka ;% N803 absorption rate constant [/d] | ||
| Pars(18) = ke ;% N803 elimination rate constant [/d] | ||
| Pars(19) = vd ;% N803 'volume of distribution'/'bioavailability' [L/kg] | ||
| Pars(20) = C50 ;% 50% N803 stimulation concentration [pM] | ||
| Pars(21) = p1 ;% E0/B0 proliferation stimulation factor [] | ||
| Pars(22) = aE1 ;% E activation stimulation factor [] | ||
| Pars(23) = aB1 ;% B activation stimulation factor [] | ||
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| Pars(24) = sE ;% R generation due to E0 activation [/d] | ||
| Pars(25) = sB ;% R generation due to B0 activation [/d] | ||
| Pars(26) = dR ;% R decay rate constant [/d] | ||
| Pars(27) = gE2 ;% E killing regulation factor [] | ||
| Pars(28) = gB2 ;% B killing regulation factor [] | ||
| Pars(29) = p2 ;% E0/B0 proliferation regulation factor [] | ||
| Pars(30) = aE2 ;% E activation regulation factor [] | ||
| Pars(31) = aB2 ;% B activation regulation factor [] | ||
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| % V E0-8 B0-2 X C R initial values | ||
| Yic = [ Vi E0 E B0 B 0 0 1 1 ] ; | ||
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| if any( [ Yic aE0 aB0 p0 gE0 gB0 sE sB ] < 0 ) | ||
| error('Negative parameters or initial values.') | ||
| end | ||
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| Y_OUT = N803_model_2(SoluTimes,DoseTimes,Pars,Yic,varargin) ; | ||
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| end |