相关论文: Irreversible evolution, obstacles in fitness lands…

Adaptation is a central topic in theoretical biology, of practical importance for analyzing drug resistance mutations. Several authors have used arguments based on extreme value theory in their work on adaptation. There are complications…

Bacteria evolve resistance to antibiotics by a multitude of mechanisms. A central, yet unsolved question is how resistance evolution affects cell growth at different drug levels. Here we develop a fitness model that predicts growth rates of…

Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anti-cancer drugs. We use a statistical physics model to study the evolution of a population of malignant…

Drug resistance is a serious public health problem that threatens to thwart our ability to treat many infectious diseases. Repeatedly, the introduction of new drugs has been followed by the evolution of resistance. In principle there are…

Evolving systems, be it an antibody repertoire in the face of mutating pathogens or a microbial population exposed to varied antibiotics, constantly search for adaptive solutions in time-varying fitness landscapes. Generalists correspond to…

Many drug delivery systems suffer from undesirable interactions with the host immune system. It has been experimentally established that covalent attachment (irreversible adsorption) of suitable macromolecules to the surface of the drug…

Fitness landscapes are central in analyzing evolution, in particular for drug resistance mutations for bacteria and virus. We show that the fitness landscapes associated with antibiotic resistance are not compatible with any of the…

Non-genetic forms of antimicrobial drug resistance can result from cell-to-cell variability that is not encoded in the genetic material. Data from recent studies also suggest that non-genetic mechanisms can facilitate the development of…

Biological evolution can be conceptualized as a search process in the space of gene sequences guided by the fitness landscape, a mapping that assigns a measure of reproductive value to each genotype. Here we discuss probabilistic models of…

Evolutionary accumulation models (EvAMs) are an emerging class of machine learning methods designed to infer the evolutionary pathways by which features are acquired. Applications include cancer evolution (accumulation of mutations),…

Human immunodeficiency virus (HIV) evolves with extraordinary rapidity. However, its evolution is constrained by interactions between mutations in its fitness landscape. Here we show that an Ising model describing these interactions,…

Biological evolution of a population is governed by the fitness landscape, which is a map from genotype to fitness. However, a fitness landscape depends on the organisms environment, and evolution in changing environments is still poorly…

The pace and unpredictability of evolution are critically relevant in a variety of modern challenges: combating drug resistance in pathogens and cancer, understanding how species respond to environmental perturbations like climate change,…

We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain…

Antimicrobial resistance is an emerging global health crisis that is undermining advances in modern medicine and, if unmitigated, threatens to kill 10 million people per year worldwide by 2050. Research over the last decade has demonstrated…

The evolution of antimicrobial resistance generally occurs in an environment where antimicrobial concentration is variable, which has dramatic consequences on the microorganisms' fitness landscape, and thus on the evolution of resistance.…

How adaptive evolution to one environmental stress improves or suppresses adaptation to another is an important problem in evolutionary biology. For instance, in microbiology, the evolution of bacteria to be resistant to different…

Epistatic interactions between mutations add substantial complexity to adaptive landscapes, and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a…

Investigating the emergence of a particular cell type is a recurring theme in models of growing cellular populations. The evolution of resistance to therapy is a classic example. Common questions are: when does the cell type first occur,…

Evolution on neutral networks of genotypes has been found in models to concentrate on genotypes with high mutational robustness, to a degree determined by the topology of the network. Here analysis is generalized beyond neutral networks to…