A5004110504- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Genomics and Phylogenetic Studies
- HIV/AIDS Research and Interventions
- Evolution and Genetic Dynamics
- Hepatitis C virus research
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- SARS-CoV-2 detection and testing
- HIV, Drug Use, Sexual Risk
- Hepatitis B Virus Studies
- Genetic diversity and population structure
- Cytomegalovirus and herpesvirus research
- Plant Virus Research Studies
- Genetics, Bioinformatics, and Biomedical Research
- Glycosylation and Glycoproteins Research
- Influenza Virus Research Studies
- vaccines and immunoinformatics approaches
- Machine Learning in Bioinformatics
- SARS-CoV-2 and COVID-19 Research
- Complex Network Analysis Techniques
- Herpesvirus Infections and Treatments
- Protein Structure and Dynamics
- Respiratory viral infections research
- Biosensors and Analytical Detection
Western University
2016-2025
British Columbia Children's Hospital
2021
AIDS Vancouver
2009-2019
University of British Columbia
2000-2019
St. Paul's Hospital
2012-2016
Simon Fraser University
2014-2016
University of California, San Diego
2004-2010
University of Cambridge
2010
VA San Diego Healthcare System
2007
Datamonkey is a popular web-based suite of phylogenetic analysis tools for use in evolutionary biology. Since the original release 2005, we have expanded options to include recently developed algorithmic methods recombination detection, fingerprinting genes, codon model selection, co-evolution between sites, identification which rapidly escape host-immune pressure and HIV-1 subtype assignment. The traditional selection also been augmented recent developments field. Here, summarize analyses...
Abstract HYpothesis testing using PHYlogenies (HyPhy) is a scriptable, open-source package for fitting broad range of evolutionary models to multiple sequence alignments, and conducting subsequent parameter estimation hypothesis testing, primarily in the maximum likelihood statistical framework. It has become popular choice characterizing various aspects process: natural selection, rates, recombination, coevolution. The 2.5 release (available from www.hyphy.org) includes completely...
Genetically diverse pathogens (such as Human Immunodeficiency virus type 1, HIV-1) are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes. Computational identification of such is helpful in surveillance, epidemiological analysis and detection novel variants, e.g., circulating recombinant forms HIV-1. A number conceptually technically different techniques have been proposed determining the subtype a query sequence, but there not...
Background. Clinically, human immunodeficiency virus type 1 (HIV-1) pol sequences are used to evaluate for drug resistance. These data can also be transmission networks and help describe factors associated with risk. Methods. HIV-1 from participants at 5 sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort 2000–2009 were analyzed genetic relatedness. Only first available sequence per participant was included. Inferred (“clusters”) defined as ≥2 ≤1.5% distance. Clusters...
Background. The diversification of human immunodeficiency virus (HIV) is shaped by its transmission history. We therefore used a population based province wide HIV drug resistance database in British Columbia (BC), Canada, to evaluate the impact clinical, demographic, and behavioral factors on rates transmission.
For infectious diseases, a genetic cluster is group of closely related infections that usually interpreted as representing recent outbreak transmission. Genetic clustering methods are becoming increasingly popular for molecular epidemiology, especially in the context HIV where there now considerable interest applying these to prioritize groups public health resources such pre-exposure prophylaxis. To date, has generally been performed with ad hoc algorithms, only some which have since...
For many disease-causing virus species, global diversity is clustered into a taxonomy of subtypes with clinical significance. In particular, the classification infections among human immunodeficiency type 1 (HIV-1) routine component management, and there are now algorithms available for this purpose. Although several these similar in accuracy speed, majority proprietary require laboratories to transmit HIV-1 sequence data over network remote servers. This potentially exposes sensitive...
SummaryBackgroundThe persistence of a replication-competent latent viral reservoir (RC-LVR) during antiretroviral therapy (ART) is barrier to the development cure for HIV-1, but role genes in influencing RC-LVR size unclear. We aimed assess whether magnitude by which HIV-1 accessory protein Nef evades adaptive immune response downregulating MHC-I or CD4, both, from surface infected cells associated with rate at people changes long-term ART (>1 year).MethodsWe conducted an exploratory cohort...
Abstract We have investigated the reduction of fitness caused by fixation new deleterious mutations in small populations within framework Fisher's geometrical model adaptation. In model, a population evolves an n‐dimensional character space with adaptive optimum at origin. The allows us to investigate compensatory mutations, which restore losses incurred other context‐dependent manner. conducted moment analysis supplemented numerical results computer simulations. mean (i.e., expected load)...
A compensatory mutation occurs when the fitness loss caused by one is remedied its epistatic interaction with a second at different site in genome. This poorly understood biological phenomenon has important implications, not only for evolutionary consequences of mutation, but also genetic complexity adaptation. We have carried out first direct experimental measurement average rate mutation. An arbitrary selection 21 missense substitutions deleterious effects on was introduced site-directed...
After acute HIV infection, CD8+ T cells are able to control viral replication a set point. This is often lost after superinfection, although the mechanism behind this remains unclear. In study, we illustrate in an HLA-B27+ subject that loss of superinfection coincides with rapid recombination events within two narrow regions Gag and Env. Screening for cell responses revealed each these sites (∼50 aa) encompassed distinct containing immunodominant CD8 epitopes (B27-KK10 Cw1-CL9 Env). Viral...
The third variable loop (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope is a principal determinant antibody neutralization and progression to AIDS. Although it undoubtedly an important target for vaccine research, extensive genetic variation in V3 remains obstacle development effective vaccine. Comparative methods that exploit abundance sequence data can detect interactions between residues rapidly evolving proteins such as HIV-1 envelope, revealing biological constraints on...
We develop a model-based phylogenetic maximum likelihood test for evidence of preferential substitution toward given residue at individual positions protein alignment--directional evolution sequences (DEPS). DEPS can identify both the target and sites evolving it, help detect selective sweeps frequency-dependent selection--scenarios that confound most existing tests selection, achieve good power accuracy on simulated data. applied to alignments representing different genomic regions...
Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied well-sampled concentrated HIV-1 epidemics wealthy countries. To direct use tools where impact is greatest, Phylogenetics And Networks for Generalized Epidemics Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges,...
Given that HIV evolution and latent reservoir establishment occur continually within-host, latently infected cells can persist long-term, the should comprise a genetically heterogeneous archive recapitulating within-host evolution. However, this has yet to be conclusively demonstrated, in part due challenges of reconstructing dynamics over long timescales. We developed phylogenetic framework reconstruct integration dates individual lineages. The first involves inference rooting...
Abstract Wastewater surveillance of coronavirus disease 2019 (COVID-19) commonly applies reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to quantify severe acute respiratory syndrome 2 (SARS-CoV-2) RNA concentrations in wastewater over time. In most applications worldwide, maximal sensitivity and specificity RT-qPCR has been achieved, part, by monitoring two or more genomic loci SARS-CoV-2. Ontario, Canada, the provincial Surveillance Initiative reports average copies...
Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during SARS-CoV-2 pandemic estimating community infection levels by qPCR. Sequencing pathogen genes genomes from wastewater adds information about genetic diversity, which can be used to identify viral lineages (including variants concern) that are circulating in local...
Highly pathogenic avian influenza (HPAI) virus H5N1 infects water and land fowl can infect cause mortality in mammals, including humans. However, HPAI strains are not equally virulent some have been shown to only mild symptoms experimental infections. Since most studies of the basis virulence mammals small scale, we undertook a meta-analysis available used Bayesian graphical models (BGM) increase power inference. We applied text-mining techniques identify 27 individual that experimentally...
Abstract Spidermonkey is a new component of the Datamonkey suite phylogenetic tools that provides methods for detecting coevolving sites from multiple alignment homologous nucleotide or amino acid sequences. It reconstructs substitution history by maximum likelihood-based methods, and then analyzes joint distribution events using Bayesian graphical models to identify significant associations among sites. Availability: publicly available both as web application at http://www.data-monkey.org...
Little is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and were evaluated PWID in Vancouver, Canada. Data derived from the Vancouver Injection Drug Users Study. Participants HCV antibody-positive at enrolment those antibody seroconversion during follow-up (1996 to 2012) tested for RNA sequenced (Core-E2 region). trees inferred using maximum likelihood analysis clusters identified ClusterPicker (90%...