相关论文: Genetic composition of an exponentially growing ce…

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…

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…

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…

The emergence of a predominant phenotype within a cell population is often triggered by a rare accumulation of DNA mutations in a single cell. For example, tumors may be initiated by a single cell in which multiple mutations cooperate to…

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…

The site frequency spectrum (SFS) is a popular summary statistic of genomic data. While the SFS of a constant-sized population undergoing neutral mutations has been extensively studied in population genetics, the rapidly growing amount of…

Single-cell experiments have revealed cell-to-cell variability in generation times and growth rates for genetically identical cells. Theoretical models relating the fluctuating generation times of single cells to the population growth rate…

The rate at which individual bacterial cells grow depends on the concentrations of cellular components such as ribosomes and proteins. These concentrations continuously fluctuate over time and are inherited from mother to daughter cells,…

We consider the evolution of populations under the joint action of mutation and differential reproduction, or selection. The population is modelled as a finite-type Markov branching process in continuous time, and the associated…

Which factors govern the evolution of mutation rates and emergence of species? Here, we address this question using a first principles model of life where population dynamics of asexual organisms is coupled to molecular properties and…

Under constant selection, each trait has a fixed fitness, and small mutation rates allow populations to efficiently exploit the optimal trait. Therefore it is reasonable to expect mutation rates will evolve downwards. However, we find this…

The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous…

Establishing a quantitative connection between the population growth rate and the generation times of single cells is a prerequisite for understanding evolutionary dynamics of microbes. However, existing theories fail to account for the…

Recent methods have been developed to map single-cell lineage statistics to population growth. Because population growth selects for exponentially rare phenotypes, these methods inherently depend on sampling large deviations from finite…

Recent evidence suggests that nongenetic (epigenetic) mechanisms play an important role at all stages of cancer evolution. In many cancers, these mechanisms have been observed to induce dynamic switching between two or more cell states,…

Here we study how mutations which change physical properties of cell proteins (stability) impact population survival and growth. In our model the genotype is presented as a set of N numbers, folding free energies of cells N proteins.…

We present an explicit solution to a classic model of cell-population growth introduced by Luria and Delbrueck 70 years ago to study the emergence of mutations in bacterial populations. In this model a wild-type population is assumed to…

Extrachromosomal DNA (ecDNA) can drive oncogene amplification, gene expression and intratumor heterogeneity, representing a major force in cancer initiation and progression. The phenomenon becomes even more intricate as distinct types of…

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.…

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…