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Nonlinear regression

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Regression analysis
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Regression analysis
Models
Estimation
Background
SeeMichaelis–Menten kinetics for details

In statistics,nonlinear regression is a form ofregression analysis in which observational data are modeled by a function which is a nonlinear combination of the model parameters and depends on one or more independent variables. The data are fitted by a method of successive approximations (iterations).

General

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In nonlinear regression, astatistical model of the form,

yf(x,β){\displaystyle \mathbf {y} \sim f(\mathbf {x} ,{\boldsymbol {\beta }})}

relates a vector ofindependent variables,x{\displaystyle \mathbf {x} }, and its associated observeddependent variables,y{\displaystyle \mathbf {y} }. The functionf{\displaystyle f} is nonlinear in the components of the vector of parametersβ{\displaystyle \beta }, but otherwise arbitrary. For example, theMichaelis–Menten model for enzyme kinetics has two parameters and one independent variable, related byf{\displaystyle f} by:[a]

f(x,β)=β1xβ2+x{\displaystyle f(x,{\boldsymbol {\beta }})={\frac {\beta _{1}x}{\beta _{2}+x}}}

This function, which is a rectangular hyperbola, isnonlinear because it cannot be expressed as alinear combination of the twoβ{\displaystyle \beta }s.

Systematic error may be present in the independent variables but its treatment is outside the scope of regression analysis. If the independent variables are not error-free, this is anerrors-in-variables model, also outside this scope.

Other examples of nonlinear functions includeexponential functions,logarithmic functions,trigonometric functions,power functions,Gaussian function, andLorentz distributions. Some functions, such as the exponential or logarithmic functions, can be transformed so that they are linear. When so transformed, standard linear regression can be performed but must be applied with caution. See§ Linearization §§ Transformation, below, for more details. In microbiology and biotechnology, nonlinear regression is used to model complex microbial growth kinetics. While simple growth follows monoauxic functions (such as the Gompertz or Boltzmann models), multiphasic (polyauxic) growth is modeled using linear combinations of these nonlinear functions. Estimating parameters for these complex models often requires robust regression techniques (e.g., using a Lorentzian loss function to mitigate outliers) and global optimization algorithms (such asDifferential evolution withL-BFGS-B) to avoid local minima and ensure biologically interpretable results.[1][2]

In general, there is no closed-form expression for the best-fitting parameters, as there is inlinear regression. Usually numericaloptimization algorithms are applied to determine the best-fitting parameters. Again in contrast to linear regression, there may be manylocal minima of the function to be optimized and even the global minimum may produce abiased estimate. In practice,estimated values of the parameters are used, in conjunction with the optimization algorithm, to attempt to find the global minimum of a sum of squares.

For details concerning nonlinear data modeling seeleast squares andnon-linear least squares.

Regression statistics

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The assumption underlying this procedure is that the model can be approximated by a linear function, namely a first-orderTaylor series:

f(xi,β)f(xi,0)+jJijβj{\displaystyle f(x_{i},{\boldsymbol {\beta }})\approx f(x_{i},0)+\sum _{j}J_{ij}\beta _{j}}

whereJij=f(xi,β)βj{\displaystyle J_{ij}={\frac {\partial f(x_{i},{\boldsymbol {\beta }})}{\partial \beta _{j}}}} are Jacobian matrix elements. It follows from this that the least squares estimators are given by

β^(JTJ)1JTy,{\displaystyle {\hat {\boldsymbol {\beta }}}\approx \mathbf {(J^{T}J)^{-1}J^{T}y} ,}comparegeneralized least squares with covariance matrix proportional to the unit matrix. The nonlinear regression statistics are computed and used as in linear regression statistics, but usingJ in place ofX in the formulas.

When the functionf(xi,β){\displaystyle f(x_{i},{\boldsymbol {\beta }})} itself is not known analytically, but needs to belinearly approximated fromn+1{\displaystyle n+1}, or more, known values (wheren{\displaystyle n} is the number of estimators), the best estimator is obtained directly from theLinear Template Fit as[3]β^=((YM~)TΩ1YM~)1(YM~)TΩ1(dYm¯){\displaystyle {\hat {\boldsymbol {\beta }}}=((\mathbf {Y{\tilde {M}}} )^{\mathsf {T}}{\boldsymbol {\Omega }}^{-1}\mathbf {Y{\tilde {M}}} )^{-1}(\mathbf {Y{\tilde {M}}} )^{\mathsf {T}}{\boldsymbol {\Omega }}^{-1}(\mathbf {d} -\mathbf {Y{\bar {m}})} } (see alsolinear least squares).

The linear approximation introducesbias into the statistics. Therefore, more caution than usual is required in interpreting statistics derived from a nonlinear model.

Ordinary and weighted least squares

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The best-fit curve is often assumed to be that which minimizes the sum of squaredresiduals. This is theordinary least squares (OLS) approach. However, in cases where the dependent variable does not have constant variance, or there are some outliers, a sum of weighted squared residuals may be minimized; seeweighted least squares. Each weight should ideally be equal to the reciprocal of the variance of the observation, or the reciprocal of the dependent variable to some power in the outlier case,[4] but weights may be recomputed on each iteration, in an iteratively weighted least squares algorithm.

Linearization

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Transformation

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Further information:Data transformation (statistics)

Some nonlinear regression problems can be moved to a linear domain by a suitable transformation of the model formulation.

For example, consider the nonlinear regression problem

y=aebxU{\displaystyle y=ae^{bx}U}

with parametersa andb and with multiplicative error termU. If we take the logarithm of both sides, this becomes

ln(y)=ln(a)+bx+u,{\displaystyle \ln {(y)}=\ln {(a)}+bx+u,}

whereu = ln(U), suggesting estimation of the unknown parameters by a linear regression of ln(y) onx, a computation that does not require iterative optimization. However, use of a nonlinear transformation requires caution. The influences of the data values will change, as will the error structure of the model and the interpretation of any inferential results. These may not be desired effects. On the other hand, depending on what the largest source of error is, a nonlinear transformation may distribute the errors in a Gaussian fashion, so the choice to perform a nonlinear transformation must be informed by modeling considerations.

ForMichaelis–Menten kinetics, the linearLineweaver–Burk plot

1v=1Vmax+KmVmax[S]{\displaystyle {\frac {1}{v}}={\frac {1}{V_{\max }}}+{\frac {K_{m}}{V_{\max }[S]}}}

of 1/v against 1/[S] has been much used. However, since it is very sensitive to data error and is strongly biased toward fitting the data in a particular range of the independent variable, [S], its use is strongly discouraged.

For error distributions that belong to theexponential family, a link function may be used to transform the parameters under theGeneralized linear model framework.

Segmentation

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Yield of mustard and soil salinity
Main article:Segmented regression

Theindependent orexplanatory variable (say X) can be split up into classes or segments andlinear regression can be performed per segment. Segmented regression withconfidence analysis may yield the result that thedependent orresponse variable (say Y) behaves differently in the various segments.[5] For example, the figure shows that thesoil salinity (X) initially exerts no influence on thecrop yield (Y) of mustard, until acritical orthreshold value (breakpoint), after which the yield is affected negatively.[6]

See also

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Notes

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  1. ^This model can also be expressed in the conventional biological notation:v=Vmax [S]Km+[S]{\displaystyle v={\frac {V_{\max }\ [\mathrm {S} ]}{K_{m}+[\mathrm {S} ]}}}

References

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  1. ^Mockaitis, Gustavo (2025). "Mono- and Polyauxic Growth Kinetics: A Semi-Mechanistic Framework for Complex Biological Dynamics".arXiv:2507.05960 [q-bio.QM].
  2. ^Mockaitis, Gustavo (2026)."Polyauxic Modeling Platform v1.0.0 (Streamlit)".doi:10.5281/zenodo.18025828.
  3. ^Britzger, Daniel (2022)."The Linear Template Fit".Eur. Phys. J. C.82 (8) 731.arXiv:2112.01548.Bibcode:2022EPJC...82..731B.doi:10.1140/epjc/s10052-022-10581-w.
  4. ^Motulsky, H.J.; Ransnas, L.A. (1987)."Fitting curves to data using nonlinear regression: a practical and nonmathematical review".The FASEB Journal.1 (5):365–374.doi:10.1096/fasebj.1.5.3315805.PMID 3315805.
  5. ^Oosterbaan, R. J. (1994)."Frequency and Regression Analysis"(PDF).Drainage Principles and Applications. Wageningen: International Institute for Land Reclamation and Improvement (ILRI). pp. 175–224.ISBN 90-70754-33-9.
  6. ^Oosterbaan, R. J. (2002)."Drainage research in farmers' fields: analysis of data"(PDF).Part of project "Liquid Gold" of the International Institute for Land Reclamation and Improvement (ILRI), Wageningen, The Netherlands.

Further reading

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  • Bethea, R. M.; Duran, B. S.; Boullion, T. L. (1985).Statistical Methods for Engineers and Scientists. New York: Marcel Dekker.ISBN 0-8247-7227-X.
  • Meade, N.; Islam, T. (1995). "Prediction Intervals for Growth Curve Forecasts".Journal of Forecasting.14 (5):413–430.doi:10.1002/for.3980140502.
  • Schittkowski, K. (2002).Data Fitting in Dynamical Systems. Boston: Kluwer.ISBN 1402010796.
  • Seber, G. A. F.; Wild, C. J. (1989).Nonlinear Regression. New York: John Wiley and Sons.ISBN 0471617601.
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