Documente Academic
Documente Profesional
Documente Cultură
Kevin D. Costa
Steven Kleinstein and Uri Hershberg
Spring 2010
Biomathematical Model
• A system of mathematical equations or
computer simulations that provides a
quantitative picture of how a complex
biological system functions under
healthy and diseased conditions.
• Physically-based equations
– Given knowledge of a governing physical process,
the desired model is derived from the underlying
theoretical equations
– Resulting model parameters have a specific
physical interpretation
Least-Squares
y
Error Minimization
xx
x
x
x
x
x
x data (xi,yi)
x x model (xi,ŷi)
Voltage [V]
3
1
y = a +bx
0
0 2 4 6 8 10
Intensity [mW]
data
data
model
N
2
E(a, b) = ∑[ yi − (a + bxi )]
i =1
Computing Model Parameters
for Linear Regression
N
2
E(a, b) = ∑[ yi − (a + bxi )]
i =1
∂E(a, b) ∂E(a, b)
=0 =0
a b
Σx i yi − n x y
b= a =y −bx
Σx 2i − n(x )2
n −1 2
sx ,y = (sy − b 2 s2x )
n−2
1 x2
sa = sx ,y +
n (n − 1)s2x
1 sx , y
sb =
n − 1 sx
Regression versus Correlation
Σ(x i − x )(yi − y )
r=
Σ(xi − x )2 Σ(yi − y ) 2
(n − 2) s2x, y
= 1−
(n − 1) s2y
Σx i yi − n x y
b=
Σx 2i − n(x )2
a =y −bx
Linearization of Nonlinear Models
[S]
• Many nonlinear equations can be V = Vmax
K m + [S]
“linearized” by selecting a suitable
change of variables
• Historically this has been a common
approach in analysis of scientific data,
€
mainly due to ease of implementation
• However, “linearization” often distorts
the error structure, violates key 1 Km 1 1
= +
assumptions, and impacts resulting V Vmax [S] Vmax
model parameter values, which may
lead to incorrect conclusions
• In our modern era of computers it is
€
usually wisest to perform nonlinear
least squares analysis when using
nonlinear inverse models adapted from Lobemeier, 2000
General Model Fitting
Nonlinear Model Fitting
• The selected model ŷ is a nonlinear
function of model parameters ak, k=1..M
yˆ i = yˆ (x i ,a)
N
• The χ2 merit function is [y i − yˆ (x i ,a)]2
χ (a) = ∑
2
2
• The gradients of χ2 with respect to i=1
σ i
plot(x_data,y_data,'bx',x_data,y_model,'r-');"
xlabel('Independent Variable (***)');"
ylabel('Dependent Variable (***)'); "
function y=model(a,x)"
global known;"
y=a(1)+a(2)*x.^2+a(3).*sin(a(4).*x) - known; % May depend on known variables!
Goodness of Fit and the
Residuals Plot
model fits residuals
• The correlation coefficient (R2) is
often used to characterize the
goodness of fit between model
and data.
• A high correlation can exist even
for a model that systematically
differs from the data.
• One must also examine the
distribution of residuals--a good
model fit should yield residuals
equally distributed along x and
normally distributed around zero
with no systematic trends
adapted from Lobemeier, 2000
y
the experimenter
• True parameters are statistically
D
realized, along with measurement (3)
DS(2)
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