Related papers: Identifying Selections Operating on HIV-1 Reverse …
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…
We introduce a new version of forward stepwise regression. Our modification finds solutions to regression problems where the selected predictors appear in a structured pattern, with respect to a predefined distance measure over the…
Motivation: HIV is difficult to treat because its virus mutates at a high rate and mutated viruses easily develop resistance to existing drugs. If the relationships between mutations and drug resistances can be determined from historical…
RNA viruses provide prominent examples of measurably evolving populations. In HIV infection, the development of drug resistance is of particular interest, because precise predictions of the outcome of this evolutionary process are a…
Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are…
HIV virus replication is a time-related process that includes several stages. Focusing on the core steps, RNA polymerase II transcripts in an early stage pre-mRNA containing regulator proteins (i.e nef,tat,rev,vif,vpr,vpu), which are…
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,…
Predicting how protein mutations affect drug binding remains a major challenge, particularly when the mutations are distal from the binding site. In this study, we introduce a coupled simulation workflow that combines long-time-scale…
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…
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…
Drug resistance to HIV-1 Protease involves accumulation of multiple mutations in the protein. Here we investigate the role of these mutations by using molecular dynamics simulations which exploit the influence of the native-state topology…
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…
People living with HIV on antiretroviral therapy often have undetectable virus levels by standard assays, but "latent" HIV still persists in viral reservoirs. Eliminating these reservoirs is the goal of HIV cure research. The quantitative…
HIV-1 protease represents an appealing system for directed enzyme re-design, since it has various different endogenous targets, a relatively simple structure and it is well studied. Recently Chaudhury and Gray (Structure (2009) 17: 1636 --…
Globally, chronic liver disease continues to be a major health concern that requires precise predictive models for prompt detection and treatment. Using the Indian Liver Patient Dataset (ILPD) from the University of California at Irvine's…
Chronic infections of the human immunodeficiency virus (HIV) create a very complex co-evolutionary process, where the virus tries to escape the continuously adapting host immune system. Quantitative details of this process are largely…
$\textbf{Background:}$ High mutability of HIV is the driving force of antiretroviral drug resistance, which represents a medical care challenge. $\textbf{Method and Model Equation:}$ To detect the mutability of each gene in the HIV-1…
Structure-based virtual screening aims to identify high-affinity ligands by estimating binding free energies between proteins and small molecules. However, the conformational flexibility of both proteins and ligands challenges conventional…
HIV-1 infection currently cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). To characterize establishment, turnover, and evolution of viral…
In this work we develop a stochastic model of acute HIV infection, based on the well-known standard model, that allows us to simulate the complex mutation pathways of HIV escape from multiple CTL responses. Under this model, we describe two…