A5014872605- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Genomics and Phylogenetic Studies
- Genetic diversity and population structure
- Evolution and Paleontology Studies
- T-cell and B-cell Immunology
- Molecular spectroscopy and chirality
- stochastic dynamics and bifurcation
- Neuroscience and Neuropharmacology Research
- Family Support in Illness
- Hepatitis C virus research
- Immune Cell Function and Interaction
- Neural dynamics and brain function
- Evolution and Genetic Dynamics
- Chromosomal and Genetic Variations
- Algebraic structures and combinatorial models
- Advanced Combinatorial Mathematics
- Endometrial and Cervical Cancer Treatments
- Psychotherapy Techniques and Applications
- Species Distribution and Climate Change
- Legal and Constitutional Studies
- Poxvirus research and outbreaks
- Topological and Geometric Data Analysis
- Optimism, Hope, and Well-being
Simon Fraser University
2012-2024
AIDS Vancouver
2016-2024
University of British Columbia
2018-2024
Pacific Biosciences (United States)
2024
University of Hawaiʻi at Mānoa
2001-2024
University of Hawaii System
1993-2024
George Washington University
2017
Foothills Medical Centre
2014-2016
Alberta Health Services
2016
Centre National de la Recherche Scientifique
2012
Phylogenetic trees and data are often stored in incompatible inconsistent formats. The outputs of software tools that contain with analysis findings not compatible each other, making it hard to integrate the results different analyses a comparative study. treeio package is designed connect phylogenetic tree input output. It supports extracting as well commonly used analytical software. can link external phylogenies merge obtained from sources, enabling phylogeny-associated disciplines an...
Synopsis Coping has attracted much attention in research as a possible mediator of the psychological impact cancer. Yet, conceptual ambiguity and methodological limitations have resulted weak contradictory findings. A major shortcoming been use designs which do not represent adequately complexity or diversity demands arise from diagnosis treatment The neglect appraisal assessment relationship between coping mental health is particular concern, given role it found to play onset maintenance...
Characterizing the genetically diverse HIV sequences that persist in reservoir despite antiretroviral therapy (ART) is critical to cure efforts. Our observations confirm proviruses persisting blood on ART, which are largely defective, broadly reflect extent of within-host evolution pre-ART. Moreover, on-ART clonal expansion not appreciably accompanied by loss distinct proviral lineages. In fact, genetic composition remained stable all but one participant, whom, after 12 years dating around...
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...
Molecular epidemiology reveals that aquaculture contributes to emergence of a fish virus at both global and local epidemic hierarchies.
Background. This study investigated whether individuals with borderline personality disorder (BPD) tend to be overgeneral in their autobiographical recall and the extent of covaries susceptibilities dissociative experiences, as expected on theoretical grounds. Methods. Twenty-three patients BPD 23 matched controls completed Autobiographical Memory Test (AMT) self-report measures depression, anxiety, trait anger experiences. Results. Participants scored significantly higher than control group...
Abstract Summary: ANGES is a suite of Python programs that allows reconstructing ancestral genome maps from the comparison organization extant-related genomes. can reconstruct for multichromosomal linear genomes and unichromosomal circular It implements methods inspired techniques developed to compute physical extant Examples cereal, amniote, yeast or bacteria are provided, computed with ANGES. Availability: freely available download at http://paleogenomics.irmacs.sfu.ca/ANGES/....
The HIV-1 reservoir consists of latently infected cells that persist despite antiretroviral therapy (ART). Elucidating the proviral genetic composition reservoir, particularly in context pre-therapy viral diversity, is therefore important to understanding formation and persistence cells. Here we investigate variants from 13 Zambian acutely-infected individuals with additional sampling for a unique comparison ART-naïve quasispecies. We identified complete transmitted/founder (TF) viruses...
Two key questions in HIV reservoir biology are whether immune-privileged tissues, such as the testes, harbor distinctive proviral populations during suppressive therapy and, if so, by what mechanism. While our results indicated that blood-testis genetic compartmentalization was reasonably common (60%), it always attributable to differential frequencies of identical sequences between sites. No blood-tissue data set retained evidence when only unique per site were considered; moreover, immune...
The HIV reservoir, which comprises diverse proviruses integrated into the genomes of infected, primarily CD4+ T cells, is main barrier to developing an effective cure. Our understanding genetics and dynamics persisting within distinct cell subsets, however, remains incomplete. Using single-genome amplification, we characterized subgenomic proviral sequences (nef region) from naive, central memory, transitional effector memory cells five HIV-infected individuals on long-term combination...
Curing HIV will require eliminating the reservoir of integrated, replication-competent proviruses that persist despite antiretroviral therapy (ART). Understanding burden, genetic diversity, and longevity persisting in diverse individuals with is critical to this goal, but these characteristics remain understudied some groups. Among them are viremic controllers-individuals who naturally suppress low levels for whom nevertheless recommended. We reconstructed within-host evolutionary histories...
Phylogenetic trees encode the evolutionary distances between species or populations. With sufficient information, these can be rescaled over time to provide estimates of dates most recent ancestors species. Here we present R program node.dating, divergence-time analysis software, which uses a maximum-likelihood method estimate internal nodes phylogenetic tree.node.dating is available as part v3.30 package ape v4.0 (cran.r-project.org). node.dating also in GitHub repository:...
Objective: Timely initiation of combination antiretroviral therapy (ART) limits latent HIV reservoir size and should also limit genetic complexity. However, the relationship between these two factors remains unclear, particularly among HIV-infected youth. Design: Retrospective analysis replication-competent clones serially isolated by limiting-dilution culture from resting CD4+ T-cell reservoirs ART-suppressed, young adult participants a historic phase I therapeutic vaccine trial...
Abstract Cophylogeny is the congruence of phylogenetic relationships between two different groups organisms due to their long‐term interaction. We investigated use tree shape distance measures quantify degree cophylogeny. implemented a reverse‐time simulation model pathogen phylogenies within fixed host tree, given cospeciation probability, switching, and speciation rates. used this evaluate 18 trees including kernel distances that we developed for labeled unlabeled trees, which branch...
ABSTRACT In order to cure human immunodeficiency virus (HIV), we need better understand the within-host evolutionary origins of small reservoir genome-intact proviruses that persist within infected cells during antiretroviral therapy (ART). Most prior studies on dynamics, however, did not discriminate from vast background defective ones. We reconstructed pre-ART HIV histories in six individuals and leveraged this information infer ages intact sampled after an average >9 years ART, along...
Abstract Hypermutated proviruses, which arise in a single Human Immunodeficiency Virus (HIV) replication cycle when host antiviral APOBEC3 proteins introduce extensive guanine to adenine mutations throughout the viral genome, persist all people living with HIV receiving antiretroviral therapy (ART). However, hypermutated sequences are routinely excluded from phylogenetic trees because their complicate inference, and as result, we know relatively little about within-host evolutionary origins...
Abstract The HIV accessory protein Nef downregulates the viral entry receptor CD4, Human Leukocyte Antigen (HLA)-A and -B molecules, Serine incorporator 5 (SERINC5) other molecules from infected cell surface, thereby promoting infectivity, replication immune evasion. nef locus also represents one of most genetically variable regions in genome, sequences undergo substantial evolution within a single individual over course infection. Few studies however have simultaneously characterized impact...
Human immunodeficiency virus (HIV) can persist as an integrated provirus, in a transcriptionally repressed state, within infected cells. This small yet enduring pool of cellular reservoirs that harbor replication-competent HIV is the main barrier to cure. Entry viral sequences into begins shortly after infection, and cells containing proviral DNA are extremely stable once suppressive antiretroviral therapy (ART) initiated. During untreated infection however, reservoir turnover likely be more...
The lung is an understudied site of HIV persistence. We isolated 898 subgenomic proviral sequences ( nef ) by single-genome approaches from blood and nine individuals on long-term suppressive antiretroviral therapy (ART), characterized genetic diversity compartmentalization using formal tests. Consistent with clonal expansion as a driver persistence, identical comprised between 8% to 86% within-host datasets, though their location (blood vs. lung) followed no consistent pattern. majority...
Abstract The complexities of viral evolution can be difficult to elucidate. Software simulating provides powerful tools for exploring hypotheses systems, especially in situations where thorough empirical data are obtain or parameters interest measure. Human immunodeficiency virus 1 (HIV-1) infection has no durable cure; this is primarily due the virus’ ability integrate into genome host cells, it remain a transcriptionally latent state. An effective cure strategy must eliminate every copy...
Abstract Human immunodeficiency virus 1 (HIV) proviruses archived in the persistent reservoir currently pose greatest obstacle to HIV cure due their evasion of combined antiretroviral therapy and ability reseed infection. Understanding dynamics is imperative for discovering a durable cure. Here, we explore Bayesian methods using software BEAST2 estimate proviral integration dates. We started with within-host longitudinal sequences collected prior therapy, along from during suppressive...
Abstract Within-host HIV populations continually diversify during untreated infection, and members of these diverse forms persist within infected cell reservoirs, even antiretroviral therapy (ART). Characterizing the viral sequences that ART is critical to cure efforts, but our knowledge on-ART proviral evolutionary dynamics remains incomplete, as does understanding differences between overall pool persisting DNA (which largely genetically defective) subset intact capable reactivating. Here,...