Waiting time models of cancer progression

Cancer progression is an evolutionary process that is driven by mutation and selection in a population of tumor cells. We discuss mathematical models of cancer progression, starting from traditional multistage theory. Each stage is associated with the occurrence of genetic alterations and their fixation in the population. We describe the accumulation of mutations using conjunctive Bayesian networks, an exponential family of waiting time models in which the occurrence of mutations is constrained to a partial temporal order. Two opposing limit cases arise if mutations either follow a linear order or occur independently. We derive exact analytical expressions for the waiting time until a specific number of mutations have accumulated in these limit cases as well as for the general conjunctive Bayesian network. Finally, we analyze a stochastic population genetics model that explicitly accounts for mutation and selection. In this model, waves of clonal expansions sweep through the population at equidistant intervals. We present an approximate analytical expression for the waiting time in this model and compare it to the results obtained for the conjunctive Bayesian networks

Structurama: Bayesian Inference of Population Structure

Structurama is a program for inferring population structure. Specifically, the program calculates the posterior probability of assigning individuals to different populations. The program takes as input a file containing the allelic information at some number of loci sampled from a collection of individuals. After reading a data file into computer memory, Structurama uses a Gibbs algorithm to sample assignments of individuals to populations. The program implements four different models: The number of populations can be considered fixed or a random variable with a Dirichlet process prior; moreover, the genotypes of the individuals in the analysis can be considered to come from a single population (no admixture) or as coming from several different populations (admixture). The output is a file of partitions of individuals to populations that were sampled by the Markov chain Monte Carlo algorithm. The partitions are sampled in proportion to their posterior probabilities. The program implements a number of ways to summarize the sampled partitions, including calculation of the ‘mean’ partition—a partition of the individuals to populations that minimizes the squared distance to the sampled partitions

Central limit theorem for multiplicative class functions on the symmetric group

Hambly, Keevash, O'Connell and Stark have proven a central limit theorem for the characteristic polynomial of a permutation matrix with respect to the uniform measure on the symmetric group. We generalize this result in several ways. We prove here a central limit theorem for multiplicative class functions on symmetric group with respect to the Ewens measure and compute the covariance of the real and the imaginary part in the limit. We also estimate the rate of convergence with the Wasserstein distance.Comment: 23 pages; the mathematics is the same as in the previous version, but there are several improvments in the presentation, including a more intuitve name for the considered function

Shift in critical temperature for random spatial permutations with cycle weights

We examine a phase transition in a model of random spatial permutations which originates in a study of the interacting Bose gas. Permutations are weighted according to point positions; the low-temperature onset of the appearance of arbitrarily long cycles is connected to the phase transition of Bose-Einstein condensates. In our simplified model, point positions are held fixed on the fully occupied cubic lattice and interactions are expressed as Ewens-type weights on cycle lengths of permutations. The critical temperature of the transition to long cycles depends on an interaction-strength parameter $\alpha$. For weak interactions, the shift in critical temperature is expected to be linear in $\alpha$ with constant of linearity $c$. Using Markov chain Monte Carlo methods and finite-size scaling, we find $c = 0.618 \pm 0.086$. This finding matches a similar analytical result of Ueltschi and Betz. We also examine the mean longest cycle length as a fraction of the number of sites in long cycles, recovering an earlier result of Shepp and Lloyd for non-spatial permutations.Comment: v2 incorporated reviewer comments. v3 removed two extraneous figures which appeared at the end of the PDF

Geometry, Scaling and Universality in the Mass Distributions in Heavy Ion Collisions

Various features of the mass yields in heavy ion collisions are studied. The mass yields are discussed in terms of iterative one dimensional discrete maps. These maps are shown to produce orbits for a monomer or for a nucleus which generate the mass yields and the distribution of cluster sizes. Simple Malthusian dynamics and non-linear Verhulst dynamics are used to illustrate the approach. Nuclear cobwebbing, attractors of the dynamics, and Lyapanov exponents are discussed for the mass distribution. The self-similar property of the Malthusian orbit offers a new variable for the study of scale invariance using power moments of the mass distribution. Correlation lengths, exponents and dimensions associated with scaling relations are developed. Fourier transforms of the mass distribution are used to obtain power spectra which are investigated for a $1/f^{\beta}$ behavior.Comment: 29 pages in REVTEX, 9 figures (available from the authors), RU-92-0

A Finitary Characterization of the Ewens Sampling Formula

As the Ewens sampling formula represents an equilibrium distribution satisfying detailed balance, some properties difficult to prove are derived in a simple way

Commitment versus persuasion in the three-party constrained voter model

In the framework of the three-party constrained voter model, where voters of two radical parties (A and B) interact with "centrists" (C and Cz), we study the competition between a persuasive majority and a committed minority. In this model, A's and B's are incompatible voters that can convince centrists or be swayed by them. Here, radical voters are more persuasive than centrists, whose sub-population consists of susceptible agents C and a fraction zeta of centrist zealots Cz. Whereas C's may adopt the opinions A and B with respective rates 1+delta_A and 1+delta_B (with delta_A>=delta_B>0), Cz's are committed individuals that always remain centrists. Furthermore, A and B voters can become (susceptible) centrists C with a rate 1. The resulting competition between commitment and persuasion is studied in the mean field limit and for a finite population on a complete graph. At mean field level, there is a continuous transition from a coexistence phase when zeta= Delta_c. In a finite population of size N, demographic fluctuations lead to centrism consensus and the dynamics is characterized by the mean consensus time tau. Because of the competition between commitment and persuasion, here consensus is reached much slower (zeta=Delta_c) than in the absence of zealots (when tau\simN). In fact, when zeta<Delta_c and there is an initial minority of centrists, the mean consensus time asymptotically grows as tau\simN^{-1/2} e^{N gamma}, where gamma is determined. The dynamics is thus characterized by a metastable state where the most persuasive voters and centrists coexist when delta_A>delta_B, whereas all species coexist when delta_A=delta_B. When zeta>=Delta_c and the initial density of centrists is low, one finds tau\simln N (when N>>1). Our analytical findings are corroborated by stochastic simulations.Comment: 25 pages, 6 figures. Final version for the Journal of Statistical Physics (special issue on the "applications of statistical mechanics to social phenomena"