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drug.m
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drug.m
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clc
clear all;
close all;
tspan = 0:1:1000;
%k1 k2 k3 k16 k34 k43 k61 k67 k76 k23 k25 k28 k89 k98 a
k=[1 1.6 0.05 0.4 0.04 0.01 0.30 0.7 0.1 0.3 0.9 0.06 0.07 0.01 0.04];
%J11 J12 J15 J18 J61 J62 J65 J68 J13 J63
J=[0.5 5.00 0.001 0.6 5.0 8.0 6.0 7 0.002 2.0];
%Km1 Km2 Km4 Km9 kp
Km=[0.5 4.0 0.3 0.005 0.05];
%phiRB phiE2F phicycD phicycDa phiAP phiPRBp phiPRBpp phiCycE phiCyca Fm
phi=[0.005 0.1 0.02300 0.030000 0.0100 0.06000 0.040000 0.06000 0.05000 0.044];
C=0;
D=0;
pars = [k J Km phi C D];
initial = [5 0 0 0.01 0 0 0 0 0.01];
figure;
%Solve for ODE at different Fm
for i=1:16
pars(40)=i*0.0005;
options = odeset('reltol',1e-6);
[t,result{i}]=ode45(@G1S_Func,tspan,initial,options,pars);
subplot(4,4,i);plot(t,result{i}); axis([0 1000 0 15]);
end
r1=result{1};r2=result{2};r3=result{3};r4=result{4};r5=result{5};
r6=result{6};r7=result{7};r8=result{8};r9=result{9};r10=result{10};
r11=result{11};r12=result{12};r13=result{13};r14=result{14};r15=result{15};
r16=result{16};%r17=result{17};r18=result{18};r19=result{19};r20=result{20};
Stability_Low=[r1(200,2),r2(200,2),r3(200,2),r4(200,2),r5(200,2),r6(200,2),r7(200,2),r8(200,2),r9(200,2),r10(200,2),r11(200,2),r12(200,2),r13(200,2),r14(200,2),r15(200,2),r16(200,2)];%,r17(200,2),r18(200,2),r19(200,2),r20(200,2)];
% Stability_High=[r1(1000,2),r2(1000,2),r3(1000,2),r4(1000,2),r5(1000,2),r6(1000,2),r7(1000,2),r8(1000,2),r9(1000,2),r10(1000,2),r11(1000,2),r12(1000,2),r13(1000,2),r14(1000,2),r15(1000,2),r16(1000,2),r17(1000,2),r18(1000,2),r19(1000,2),r20(1000,2)];
Stability_High=[r1(800,2),r2(800,2),r3(800,2),r4(800,2),r5(800,2),r6(800,2),r7(800,2),r8(800,2),r9(800,2),r10(800,2),r11(800,2),r12(800,2),r13(800,2),r14(800,2),r15(800,2),r16(800,2)];%,r17(800,2),r18(800,2),r19(800,2),r20(800,2)];
Fm=zeros(1,16);
for i=1:16
Fm(i)=i*0.0005;
end
%Constitutive Overspression of Cyclin D w/double degradation rate
C=0;
D=0.02;
k(10)=0.28;
pars = [k J Km phi C D];
pars(33)=0.04; %changing the degradation rate for cyclin D_i
pars(34)=0.05; %changing the degradation rate for cyclin D_a
figure;
for i=1:16
pars(40)=i*0.0005;
options = odeset('reltol',1e-6);
[t,result{i}]=ode45(@G1S_Func,tspan,initial,options,pars);
subplot(4,4,i);plot(t,result{i}); axis([0 1000 0 15]);
end
r1=result{1};r2=result{2};r3=result{3};r4=result{4};r5=result{5};
r6=result{6};r7=result{7};r8=result{8};r9=result{9};r10=result{10};
r11=result{11};r12=result{12};r13=result{13};r14=result{14};r15=result{15};
r16=result{16};
Stability_LowD(1,:)=[r1(200,2),r2(200,2),r3(200,2),r4(200,2),r5(200,2),r6(200,2),r7(200,2),r8(200,2),r9(200,2),r10(200,2),r11(200,2),r12(200,2),r13(200,2),r14(200,2),r15(200,2),r16(200,2)];
Stability_HighD(1,:)=[r1(800,2),r2(800,2),r3(800,2),r4(800,2),r5(800,2),r6(800,2),r7(800,2),r8(800,2),r9(800,2),r10(800,2),r11(800,2),r12(800,2),r13(800,2),r14(800,2),r15(800,2),r16(800,2)];
%Constitutive Overspression of Cyclin D
C=0;
D=0.02;
k(10)=0.28;
pars = [k J Km phi C D];
pars(33)=0.023; %changing the degradation rate for cyclin D_i
pars(34)=0.03; %changing the degradation rate for cyclin D_a
figure;
for i=1:16
pars(40)=i*0.0005;
options = odeset('reltol',1e-6);
[t,result{i}]=ode45(@G1S_Func,tspan,initial,options,pars);
subplot(4,4,i);plot(t,result{i}); axis([0 1000 0 15]);
end
r1=result{1};r2=result{2};r3=result{3};r4=result{4};r5=result{5};
r6=result{6};r7=result{7};r8=result{8};r9=result{9};r10=result{10};
r11=result{11};r12=result{12};r13=result{13};r14=result{14};r15=result{15};
r16=result{16};
Stability_LowD(2,:)=[r1(200,2),r2(200,2),r3(200,2),r4(200,2),r5(200,2),r6(200,2),r7(200,2),r8(200,2),r9(200,2),r10(200,2),r11(200,2),r12(200,2),r13(200,2),r14(200,2),r15(200,2),r16(200,2)];
Stability_HighD(2,:)=[r1(800,2),r2(800,2),r3(800,2),r4(800,2),r5(800,2),r6(800,2),r7(800,2),r8(800,2),r9(800,2),r10(800,2),r11(800,2),r12(800,2),r13(800,2),r14(800,2),r15(800,2),r16(800,2)];
%Constitutive Overspression of Cyclin D
% C=0;
% D=0.02;
%
% k(10)=0.28;
%
% pars = [k J Km phi C D];
% pars(34)=0.075; %changing the degradation rate for cyclin D_a
%
% figure;
%
% for i=1:16
% pars(40)=i*0.0005;
% options = odeset('reltol',1e-6);
% [t,result{i}]=ode45(@G1S_Func,tspan,initial,options,pars);
% subplot(4,4,i);plot(t,result{i}); axis([0 1000 0 15]);
% end
%
% r1=result{1};r2=result{2};r3=result{3};r4=result{4};r5=result{5};
% r6=result{6};r7=result{7};r8=result{8};r9=result{9};r10=result{10};
% r11=result{11};r12=result{12};r13=result{13};r14=result{14};r15=result{15};
% r16=result{16};
%
% Stability_LowDE=[r1(200,2),r2(200,2),r3(200,2),r4(200,2),r5(200,2),r6(200,2),r7(200,2),r8(200,2),r9(200,2),r10(200,2),r11(200,2),r12(200,2),r13(200,2),r14(200,2),r15(200,2),r16(200,2)];
% Stability_HighDE=[r1(800,2),r2(800,2),r3(800,2),r4(800,2),r5(800,2),r6(800,2),r7(800,2),r8(800,2),r9(800,2),r10(800,2),r11(800,2),r12(800,2),r13(800,2),r14(800,2),r15(800,2),r16(800,2)];
%% Generate Bifurcation plot
figure; axis([0 0.0005*16 0 15]);
subplot(2,1,1);plot(Fm,Stability_Low,Fm(7:16),Stability_High(7:16),'b');
xlabel('Fm');ylabel('E2F1');grid on;title('Bifurcation without Overexpression of Cyclin E & D')
subplot(2,1,2);plot(Fm(8:16),Stability_HighD(1,8:16),'r',Fm,Stability_HighD(2,:),'g');
legend('increased degradation','normal degradation')
hold on
plot(Fm,Stability_LowD(1,:),'r',Fm,Stability_LowD(2,:),'g')
xlabel('Fm');ylabel('E2F1');grid on;title('Bifurcation with Overexpression of Cyclin D with increasing degradation rate')
% subplot(3,1,3);plot(Fm,Stability_LowDE,Fm(1:16),Stability_HighDE(1:16));
% xlabel('Fm');ylabel('E2F1');grid on;title('Bifurcation with Overexpression of Cyclin D at phi_CycD_a-0.075')