相关论文: Longitudinal Antigenic Sequences and Sites from In…
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,…
The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an…
The rates of escape and reversion in response to selection pressure arising from the host immune system, notably the cytotoxic T-lymphocyte (CTL) response, are key factors determining the evolution of HIV. Existing methods for estimating…
Viruses evolve in the background of host immune systems that exert selective pressure and drive viral evolutionary trajectories. This interaction leads to different evolutionary patterns in antigenic space. Examples observed in nature…
Cytotoxic T-lymphocytes (CTLs) recognize viral protein fragments displayed by major histocompatibility complex (MHC) molecules on the surface of virally infected cells and generate an anti-viral response that can kill the infected cells.…
Intrapatient HIV-1 evolution is dominated by selection on the protein level in the arms race with the adaptive immune system. When cytotoxic CD8+ T-cells or neutralizing antibodies target a new epitope, the virus often escapes via…
Common deep learning approaches for antibody engineering focus on modeling the marginal distribution of sequences. By treating sequences as independent samples, however, these methods overlook affinity maturation as a rich and largely…
Understanding how genetic changes allow emerging virus strains to escape the protection afforded by vaccination is vital for the maintenance of effective vaccines. In the current work, we use structural and phylogenetic differences between…
During an infection, HIV experiences strong selection by immune system T cells. Recent experimental work has shown that MHC escape mutations form an important pathway for HIV to avoid such selection. In this paper, we study a model of MHC…
The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the…
The evolution of drug resistance in HIV occurs by the fixation of specific, well-known, drug-resistance mutations, but the underlying population genetic processes are not well understood. By analyzing within-patient longitudinal sequence…
In this paper we study intra-host viral adaptation by antigenic cooperation - a mechanism of immune escape that serves as an alternative to the standard mechanism of escape by continuous genomic diversification and allows to explain a…
Mutational escape from vaccine induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic…
Viral deep-sequencing data play a crucial role toward understanding disease transmission network flows, because the higher resolution of these data compared to standard Sanger sequencing provide evidence into the direction of infectious…
We present a novel model that describes the within-host evolutionary dynamics of parasites undergoing antigenic variation. The approach uses a multi-type branching process with two types of entities defined according to their relationship…
The origin of the unusual incubation period distribution in the development of AIDS is largely unresolved. A key factor in understanding the observed distribution of latency periods, as well as the occurrence of infected individuals not…
Following transmission, HIV-1 evolves into a diverse population, and next generation sequencing enables us to detect variants occurring at low frequencies. Studying viral evolution at the level of whole genomes was hitherto not possible…
Selective sweeps are typically associated with a local reduction of genetic diversity around the adaptive site. However, selective sweeps can also quickly carry neutral mutations to observable population frequencies if they arise early in a…
We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the…
Somatic variants can be used as lineage markers for the phylogenetic reconstruction of cancer evolution. Since somatic phylogenetics is complicated by sample heterogeneity, novel specialized tree-building methods are required for cancer…