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The purpose of this study is to use the method of lines to solve the two-dimensional nonlinear advection–diffusion–reaction equation with variable coefficients.

The strictly positive definite radial basis functions collocation method together with the decomposition of the interpolation matrix is used to turn the problem into a system of nonlinear first-order differential equations. Then a numerical solution of this system is computed by changing in the classical fourth-order Runge–Kutta method as well.

Several test problems are provided to confirm the validity and efficiently of the proposed method.

For the first time, some famous examples are solved by using the proposed high-order technique.