Affiliation:
1. Center for Applied Mathematics, Cornell University, Ithaca, United States
2. Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, United States
3. Department of Radiation Oncology, Cleveland Clinic, Cleveland, United States
Abstract
The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dynamics on graphs. For simple models of a mutant or pathogen invading a network-structured population of healthy cells, we show that skewed distributions of incubation periods emerge for a wide range of assumptions about invader fitness, competition dynamics, and network structure. The skewness stems from stochastic mechanisms associated with two classic problems in probability theory: the coupon collector and the random walk. Unlike previous explanations that rely crucially on heterogeneity, our results hold even for homogeneous populations. Thus, we predict that two equally healthy individuals subjected to equal doses of equally pathogenic agents may, by chance alone, show remarkably different time courses of disease.
Funder
National Science Foundation
National Institutes of Health
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Reference29 articles.
1. The distribution of incubation periods of neoplastic diseases;Armenian;American Journal of Epidemiology,1974
2. When the mean is not enough: Calculating fixation time distributions in birth-death processes;Ashcroft;Physical Review E,2015
3. Asymptotic distributions for the coupon collector's problem;Baum;The Annals of Mathematical Statistics,1965
4. Differentiation of types of poliomyelitis viruses III. The grouping of fourteen strains Into three basic immunological types;Bodian;American Journal of Hygiene,1949
Cited by
24 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献