A5060811249- HIV Research and Treatment
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Evolution and Genetic Dynamics
- Genetic diversity and population structure
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- vaccines and immunoinformatics approaches
- Genetic Neurodegenerative Diseases
- Cancer Genomics and Diagnostics
- Machine Learning in Bioinformatics
- Genomics and Rare Diseases
- Speech and dialogue systems
- Topic Modeling
- Social Robot Interaction and HRI
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Music and Audio Processing
- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
- Speech Recognition and Synthesis
- Hepatitis B Virus Studies
- HIV, Drug Use, Sexual Risk
- COVID-19 epidemiological studies
- Hepatitis C virus research
Illumina (United Kingdom)
2023
Illumina (United States)
2017-2022
Stellenbosch University
2002-2017
University of California, San Diego
2012-2017
The University of Texas Southwestern Medical Center
2016
University of Cape Town
2005-2008
University of the Western Cape
2005
South African National Biodiversity Institute
2005
University of Cambridge
2002
The imprint of natural selection on protein coding genes is often difficult to identify because frequently transient or episodic, i.e. it affects only a subset lineages. Existing computational techniques, which are designed sites subject pervasive selection, may fail recognize where episodic: large proportion positively selected sites. We present mixed effects model evolution (MEME) that capable identifying instances both episodic and positive at the level an individual site. Using empirical...
Model-based analyses of natural selection often categorize sites into a relatively small number site classes. Forcing each to belong one these classes places unrealistic constraints on the distribution parameters, which can result in misleading inference due model misspecification. We present an approximate hierarchical Bayesian method using Markov chain Monte Carlo (MCMC) routine that ensures robustness against misspecification by averaging over large predefined This leaves parameters...
Over the past two decades, comparative sequence analysis using codon-substitution models has been honed into a powerful and popular approach for detecting signatures of natural selection from molecular data. A substantial body work focused on developing class "branch-site" which permit selective pressures sequences, quantified by ω ratio, to vary among both codon sites individual branches in phylogeny. We develop present method this class, adaptive branch-site random effects likelihood...
Relaxation of selective strength, manifested as a reduction in the efficiency or intensity natural selection, can drive evolutionary innovation and presage lineage extinction loss function. Mechanisms through which selection be relaxed range from removal an existing constraint to effective population size. Standard methods for estimating strength extent purifying positive molecular sequence data are not suitable detecting because they lack power mistake increase relaxation both selection....
We present BUSTED, a new approach to identifying gene-wide evidence of episodic positive selection, where the non-synonymous substitution rate is transiently greater than synonymous rate. BUSTED can be used either on an entire phylogeny (without requiring priori hypothesis regarding which branches are under selection) or pre-specified subset foreground lineages (if suitable available). Selection modeled as varying stochastically over and sites, we propose computationally inexpensive metric...
Adaptive evolution frequently occurs in episodic bursts, localized to a few sites gene, and small number of lineages phylogenetic tree. A popular class "branch-site" evolutionary models provides statistical framework search for evidence such selection. For computational tractability, current branch-site unrealistically assume that all branches the tree can be partitioned priori into two rigid classes—"foreground" are allowed undergo diversifying selective bursts "background" negatively...
We describe a novel computational method for genotyping repeats using sequence graphs. This addresses the long-standing need to accurately genotype medically important loci containing adjacent other variants or imperfect DNA such as polyalanine repeats. Here we introduce new version of our repeat software, ExpansionHunter, that uses this perform targeted broad class loci.ExpansionHunter is implemented in C++ and available under Apache License Version 2.0. The source code, documentation,...
Sexually transmitted infections spread across contact networks. Partner elicitation and notification are commonly used public health tools to identify, notify, offer testing persons linked in these For HIV-1, a rapidly evolving pathogen with low per-contact transmission rates, viral genetic sequences an additional source of data that can be infer or refine networks.The New York City Department Health Mental Hygiene interviews individuals newly diagnosed HIV elicits names sexual injection...
Backtracking a pandemic Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have had history of abortive human infections before variant established productive enough infection to create transmission chain with potential. Therefore, the Wuhan cluster identified in late December 2019 not represented initiating event. Pekar et al. used genome data collected from early cases COVID-19 combined molecular clock inference and epidemiological simulation estimate when most successful...
Abstract Motivation: Accurate detection of positive Darwinian selection can provide important insights to researchers investigating the evolution pathogens. However, many pathogens (particularly viruses) undergo frequent recombination and phylogenetic methods commonly applied detect have been shown give misleading results when recombining sequences. We propose a method that makes maximum likelihood inference robust presence recombination. This is achieved by allowing tree topologies branch...
Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions years. The primate simplex viruses exemplify this pattern virus-host codivergence, at a minimum, as far back the most recent common ancestor New World monkeys, Old apes. Humans are only species known to be infected two distinct herpes viruses: HSV-1 HSV-2. Human ubiquitous, over two-thirds human population by least one virus. Here, we investigated whether additional virus is result ancient...
Abstract Background Expansions of short tandem repeats are the cause many neurogenetic disorders including familial amyotrophic lateral sclerosis, Huntington disease, and others. Multiple methods have been recently developed that can identify repeat expansions in whole genome or exome sequencing data. Despite widely recognized need for visual assessment variant calls clinical settings, current computational tools lack ability to produce such visualizations expansions. Expanded difficult...
Codon models of evolution have facilitated the interpretation selective forces operating on genomes. These models, however, assume a single rate non-synonymous substitution irrespective nature amino acids being exchanged. Recent developments shown that which allow for acid pairs to independent rates offer improved fit over models. However, these approaches been limited by necessity large alignments in their estimation. An alternative approach is between can be subdivided into classes,...
Standard genotypic antiretroviral resistance testing, performed by bulk sequencing, does not readily detect variants that comprise <20% of the circulating HIV-1 RNA population. Nevertheless, it is valuable in selecting an regimen after failure. In patients with poor adherence, resistant may reach this threshold. Therefore, deep sequencing would be potentially for detecting minority variants. We compared and to drug at time a second-line protease inhibitor (PI)-based Eligibility criteria were...
The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated (VE) 31% for protecting low-risk Thai volunteers against acquisition HIV-1. impact vaccine-induced immune responses can be investigated through sieve analysis HIV-1 breakthrough infections (infected and placebo recipients). A V1/V2-targeted comparison genomes viruses identified two V2 amino acid sites that differed between groups. Here we extended V1/V2 to entire genome using array methods based on...
To design effective eradication strategies, it may be necessary to target HIV reservoirs in anatomic compartments other than blood. This study examined RNA rebound following interruption of antiretroviral therapy (ART) blood and cerebrospinal fluid (CSF) determine whether the central nervous system (CNS) might serve as an independent source resurgent viral replication. Paired CSF samples were collected longitudinally from 14 chronically HIV-infected individuals undergoing ART interruption....
Over time, natural selection molds every gene into a unique mosaic of sites evolving rapidly or resisting change-an "evolutionary fingerprint" the gene. Aspects this evolutionary fingerprint, such as site-specific ratio nonsynonymous to synonymous substitution rates (dN/dS), are commonly used identify genetic features potential biological interest; however, no framework exists for comparing fingerprints between genes. We hypothesize that protein-coding genes with similar protein structure...
Markov models of codon substitution are powerful inferential tools for studying biological processes such as natural selection and preferences in amino acid substitution. The equilibrium character distributions these almost always estimated using nucleotide frequencies observed a sequence alignment, primarily matter historical convention. In this note, we demonstrate that popular class estimators biased, bias has an adverse effect on goodness fit estimates rates. We propose "corrected"...
Since its identification in 1983, HIV-1 has been the focus of a research effort unprecedented scope and difficulty, whose ultimate goals — cure vaccine – remain elusive. One fundamental challenges accomplishing these is tremendous genetic variability virus, with some genes differing at as many 40% nucleotide positions among circulating strains. Because this, bases viral phenotypes, most notably susceptibility to neutralization by particular antibody, are difficult identify computationally....
This paper describes a method for automatic design of human-computer dialogue strategies by means reinforcement learning, using simulation tool to model the user behaviour and system recognition performance. To authors' knowledge this is first application detailed problem. The trained on corpus real data. Compared direct state transition modelling, it has major advantage that different space representations can be studied without collecting more training data. We applied Q-learning with...
A popular approach to detecting positive selection is estimate the parameters of a probabilistic model codon evolution and perform inference based on its maximum likelihood parameter values. This has been evaluated intensively in number simulation studies found be robust when available data set large. However, uncertainties estimated values can lead errors inference, especially small or there insufficient divergence between sequences. We introduce Bayesian comparison infer whether sequence...
Host immune responses against infectious pathogens exert strong selective pressures favouring the emergence of escape mutations that prevent recognition. Escape within or flanking functionally conserved epitopes can occur at a significant cost to pathogen in terms its ability replicate effectively. Such come under pressure revert wild type hosts do not mount an response epitope. Amino acid positions exhibiting this pattern and reversion are interest because they tend coincide with control...