Time Inhomogeneous Mutation Models with Birth Date Dependence

Time Inhomogeneous Mutation Models with Birth Date Dependence The classic Luria–Delbrück model for fluctuation analysis is extended 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. In particular, it is possible to consider subprobability distributions and to model non-exponential growth. The extended model leads to a family of probability distributions which depend on the expected number of mutations, the death probability of mutant cells, and the split instant distributions of normal and mutant cells. This is deduced from the Bellman–Harris integral equation, written for the birth date inhomogeneous case. A new theorem of convergence for the final mutant counts is proved, using an analytic method. Particular examples like the Haldane model or the case where hazard functions of the split-instant distributions are proportional are studied. The Luria–Delbrück distribution with cell deaths is recovered. A computation algorithm for the probabilities is provided. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Bulletin of Mathematical Biology Springer Journals

Time Inhomogeneous Mutation Models with Birth Date Dependence

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Publisher
Springer Journals
Copyright
Copyright © 2017 by Society for Mathematical Biology
Subject
Mathematics; Mathematical and Computational Biology; Life Sciences, general; Cell Biology
ISSN
0092-8240
eISSN
1522-9602
D.O.I.
10.1007/s11538-017-0357-3
Publisher site
See Article on Publisher Site

Abstract

The classic Luria–Delbrück model for fluctuation analysis is extended 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. In particular, it is possible to consider subprobability distributions and to model non-exponential growth. The extended model leads to a family of probability distributions which depend on the expected number of mutations, the death probability of mutant cells, and the split instant distributions of normal and mutant cells. This is deduced from the Bellman–Harris integral equation, written for the birth date inhomogeneous case. A new theorem of convergence for the final mutant counts is proved, using an analytic method. Particular examples like the Haldane model or the case where hazard functions of the split-instant distributions are proportional are studied. The Luria–Delbrück distribution with cell deaths is recovered. A computation algorithm for the probabilities is provided.

Journal

Bulletin of Mathematical BiologySpringer Journals

Published: Oct 18, 2017

References

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