Related papers: The waiting time for m mutations
We consider the population genetics problem: how long does it take before some member of the population has $m$ specified mutations? The case $m=2$ is relevant to onset of cancer due to the inactivation of both copies of a tumor suppressor…
The appearance of cancer in a tissue is thought to be the result of two or more successive mutations. We propose a stochastic model that allows for an exact computation of the distribution of the waiting time for a second mutation. This…
Motivated by models of cancer formation in which cells need to acquire $k$ mutations to become cancerous, we consider a spatial population model in which the population is represented by the $d$-dimensional torus of side length $L$.…
Stochastic models of sequential mutation acquisition are widely used to quantify cancer and bacterial evolution. Across manifold scenarios, recurrent research questions are: how many cells are there with $n$ alterations, and how long will…
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…
We consider a model of a population of fixed size $N$ undergoing selection. Each individual acquires beneficial mutations at rate $\mu_N$, and each beneficial mutation increases the individual's fitness by $s_N$. Each individual dies at…
We consider a spatial model of cancer in which cells are points on the $d$-dimensional torus $\mathcal{T}=[0,L]^d$, and each cell with $k-1$ mutations acquires a $k$th mutation at rate $\mu_k$. We will assume that the mutation rates $\mu_k$…
We consider the accumulation of beneficial and deleterious mutations in large asexual populations. The rate of adaptation is affected by the total mutation rate, proportion of beneficial mutations and population size $N$. We show that…
We aim to understand the evolution of the genetic composition of cancer cell populations. To achieve this, we consider an individual-based model representing a cell population where cells divide, die and mutate along the edges of a finite…
We propose a one mutation model for cancer with a mutation rate that increases with time. Under rather general hypotheses the number of mutations is necessarily a (non homogeneous) Poisson process with the prescribed mutation rate. We show…
Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, $K$, at which these substitutions accumulate in the population coincides with the…
We study large deviation events in the timing of disease recurrence. In particular, we are interested in modeling cancer treatment failure due to mutation-induced drug resistance. We first present a two-type branching process model of this…
Metastasis, the spread of cancer cells from a primary tumor to secondary location(s) in the human organism, is the ultimate cause of death for the majority of cancer patients. That is why, it is crucial to understand metastases evolution in…
We introduce and analyze a waiting time model for the accumulation of genetic changes. The continuous time conjunctive Bayesian network is defined by a partially ordered set of mutations and by the rate of fixation of each mutation. The…
We study a general setting of neutral evolution in which the population is of finite, constant size and can have spatial structure. Mutation leads to different genetic types ("traits"), which can be discrete or continuous. Under minimal…
In order to analyze data from cancer genome sequencing projects, we need to be able to distinguish causative, or "driver," mutations from "passenger" mutations that have no selective effect. Toward this end, we prove results concerning the…
Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis.…
Mutations can arise from the chance misincorporation of nucleotides during DNA replication or from DNA lesions that are not repaired correctly. We introduce a model that relates the source of mutations to their accumulation with cell…
Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the…
In this article a generalized mathematical model describing the interactions between malignant tumour and immune system with discrete time delay incorporated into the system is considered. Time delay represents the time required to generate…