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The classic Luria–Delbrück model can be interpreted as a Poisson compound (number of mutations) of exponential mixtures (developing time of mutant clones) of geometric distributions (size of a clone in a given time). This “three-ingredients” approach is generalized in this paper to the case where the split instant distributions of cells are not i.i.d. : the lifetime of each cell is assumed to depend on its birth date. This model takes also into account cell deaths and non-exponentially distributed lifetimes. Previous results on the convergence of the distribution of mutant counts are recovered. The particular case where the instantaneous division rates of normal and mutant cells are proportional is studied. The classic Luria–Delbrück and Haldane models are recovered. Probability computations and simulation algorithms are provided. Robust estimation methods developed for the classic mutation models are adapted to the new model: their properties of consistency and asymptotic normality remain true; their asymptotic variances are computed. Finally, the estimation biases induced by considering classic mutation models instead of an inhomogeneous model are studied with simulation experiments. [ABSTRACT FROM AUTHOR]

Abstract: Computational simulation models can provide a way of understanding and predicting insect population dynamics and evolution of resistance, but the usefulness of such models depends on generating or estimating the values of key parameters. In this paper, we describe four numerical algorithms generating or estimating key parameters for simulating four different processes within such models. First, we describe a novel method to generate an offspring genotype table for one- or two-locus genetic models for simulating evolution of resistance, and how this method can be extended to create offspring genotype tables for models with more than two loci. Second, we describe how we use a generalized inverse matrix to find a least-squares solution to an over-determined linear system for estimation of parameters in probit models of kill rates. This algorithm can also be used for the estimation of parameters of Freundlich adsorption isotherms. Third, we describe a simple algorithm to randomly select initial frequencies of genotypes either without any special constraints or with some pre-selected frequencies. Also we give a simple method to calculate the “stable” Hardy–Weinberg equilibrium proportions that would result from these initial frequencies. Fourth we describe how the problem of estimating the intrinsic rate of natural increase of a population can be converted to a root-finding problem and how the bisection algorithm can then be used to find the rate. We implemented all these algorithms using MATLAB and Python code; the key statements in both codes consist of only a few commands and are given in the appendices. The results of numerical experiments are also provided to demonstrate that our algorithms are valid and efficient. [Copyright &y& Elsevier]