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Article ; Online: Machine Learning Prediction and Phyloanatomic Modeling of Viral Neuroadaptive Signatures in the Macaque Model of HIV-Mediated Neuropathology.

Ramirez-Mata, Andrea S / Ostrov, David / Salemi, Marco / Marini, Simone / Magalis, Brittany Rife

2023 , Page(s) e0308622

Abstract: In human immunodeficiency virus (HIV) infection, virus replication in and adaptation to the central nervous system (CNS) can result in neurocognitive deficits in approximately 25% of patients with unsuppressed viremia. While no single viral mutation can ... ...

Abstract	In human immunodeficiency virus (HIV) infection, virus replication in and adaptation to the central nervous system (CNS) can result in neurocognitive deficits in approximately 25% of patients with unsuppressed viremia. While no single viral mutation can be agreed upon as distinguishing the neuroadapted population, earlier studies have demonstrated that a machine learning (ML) approach could be applied to identify a collection of mutational signatures within the virus envelope glycoprotein (Gp120) predictive of disease. The S[imian]IV-infected macaque is a widely used animal model of HIV neuropathology, allowing in-depth tissue sampling infeasible for human patients. Yet, translational impact of the ML approach within the context of the macaque model has not been tested, much less the capacity for early prediction in other, noninvasive tissues. We applied the previously described ML approach to prediction of SIV-mediated encephalitis (SIVE) using
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.03086-22
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Article ; Online: Contrast-FEL-A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches.

Kosakovsky Pond, Sergei L / Wisotsky, Sadie R / Escalante, Ananias / Magalis, Brittany Rife / Weaver, Steven

Molecular biology and evolution

2020 Volume 38, Issue 3, Page(s) 1184–1198

Abstract: A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach ...

Abstract	A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach is to perform separate analyses on subsets of sequences and compare parameter estimates in a post hoc fashion. This approach is statistically suboptimal and not always applicable. Here, we develop a simple extension of a popular fixed effects likelihood method in the context of codon-based evolutionary phylogenetic maximum likelihood testing, Contrast-FEL. It is suitable for identifying individual alignment sites where any among the K≥2 sets of branches in a phylogenetic tree have detectably different ω ratios, indicative of different selective regimes. Using extensive simulations, we show that Contrast-FEL delivers good power, exceeding 90% for sufficiently large differences, while maintaining tight control over false positive rates, when the model is correctly specified. We conclude by applying Contrast-FEL to data from five previously published studies spanning a diverse range of organisms and focusing on different evolutionary questions.
MeSH term(s)	Brassicaceae/genetics ; Cytochromes b/genetics ; Genetic Techniques ; HIV Reverse Transcriptase/genetics ; Haemosporida/genetics ; Phylogeny ; Rhodopsin/genetics ; Ribulose-Bisphosphate Carboxylase/genetics ; Selection, Genetic ; Trichomes/genetics
Chemical Substances	Rhodopsin (9009-81-8) ; Cytochromes b (9035-37-4) ; reverse transcriptase, Human immunodeficiency virus 1 (EC 2.7.7.-) ; HIV Reverse Transcriptase (EC 2.7.7.49) ; Ribulose-Bisphosphate Carboxylase (EC 4.1.1.39)
Language	English
Publishing date	2020-10-16
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Validation Study
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msaa263
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Article ; Online: Neutral Theory and Rapidly Evolving Viral Pathogens.

Frost, Simon D W / Magalis, Brittany Rife / Kosakovsky Pond, Sergei L

Molecular biology and evolution

2018 Volume 35, Issue 6, Page(s) 1348–1354

Abstract: The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, ... ...

Abstract	The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.
MeSH term(s)	Drug Resistance, Viral/genetics ; Evolution, Molecular ; Genetic Drift ; Genetic Fitness ; Genetic Variation ; HIV-1/genetics ; Influenza A virus/genetics
Keywords	covid19
Language	English
Publishing date	2018-04-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msy088
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Article ; Online: Origin and dissemination of hepatitis B virus genotype C in East Asia revealed by phylodynamic analysis and historical correlates.

Lin, Serena Y C / Magalis, Brittany Rife / Salemi, Marco / Liu, Hsin-Fu

Journal of viral hepatitis

2018 Volume 26, Issue 1, Page(s) 145–154

Abstract: Hepatitis B virus disease progression in East Asia is most frequently associated with genotype C (HBV/C). The increasing availability of HBV/C genetic sequences and detailed annotations provides an opportunity to investigate the epidemiological factors ... ...

Abstract	Hepatitis B virus disease progression in East Asia is most frequently associated with genotype C (HBV/C). The increasing availability of HBV/C genetic sequences and detailed annotations provides an opportunity to investigate the epidemiological factors underlying its evolutionary history. In this study, the Bayesian phylogeography framework was used to investigate the origins and patterns in spatial dissemination of HBV/C by analyzing East Asian sequences obtained from 1992 to 2010. The most recent common ancestor of HBV/C was traced back to the early 1900s in China, where it eventually diverged into two major lineages during the 1930s-1960s that gave rise to distinct epidemic waves spreading exponentially to other East Asian countries and the USA. Demographic inference of viral effective population size over time indicated similar dynamics for both lineages, characterized by exponential growth since the early 1980s, followed by a significant bottleneck in 2003 and another increase after 2004. Although additional factors cannot be ruled out, we provide evidence to suggest this bottleneck was the result of limited human movement from/to China during the SARS outbreak in 2003. This is the first extensive evolutionary study of HBV/C in East Asia as well as the first to assess more realistic spatial ecological influences between co-circulating infectious diseases.
MeSH term(s)	China/epidemiology ; DNA, Viral/genetics ; Evolution, Molecular ; Asia, Eastern/epidemiology ; Gene Flow ; Genetic Variation ; Genotype ; Hepatitis B/epidemiology ; Hepatitis B/history ; Hepatitis B/transmission ; Hepatitis B virus/genetics ; History, 20th Century ; History, 21st Century ; Humans ; Phylogeny ; Phylogeography ; Population Dynamics ; Sequence Analysis, DNA ; United States/epidemiology
Chemical Substances	DNA, Viral
Keywords	covid19
Language	English
Publishing date	2018-10-17
Publishing country	England
Document type	Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/jvh.13006
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Article: Differing impacts of global and regional responses on SARS-CoV-2 transmission cluster dynamics.

Magalis, Brittany Rife / Ramirez-Mata, Andrea / Zhukova, Anna / Mavian, Carla / Marini, Simone / Lemoine, Frederic / Prosperi, Mattia / Gascuel, Olivier / Salemi, Marco

bioRxiv : the preprint server for biology

2020

Abstract: Although the global response to COVID-19 has not been entirely unified, the opportunity arises to assess the impact of regional public health interventions and to classify strategies according to their outcome. Analysis of genetic sequence data gathered ... ...

Abstract	Although the global response to COVID-19 has not been entirely unified, the opportunity arises to assess the impact of regional public health interventions and to classify strategies according to their outcome. Analysis of genetic sequence data gathered over the course of the pandemic allows us to link the dynamics associated with networks of connected individuals with specific interventions. In this study, clusters of transmission were inferred from a phylogenetic tree representing the relationships of patient sequences sampled from December 30, 2019 to April 17, 2020. Metadata comprising sampling time and location were used to define the global behavior of transmission over this earlier sampling period, but also the involvement of individual regions in transmission cluster dynamics. Results demonstrate a positive impact of international travel restrictions and nationwide lockdowns on global cluster dynamics. However, residual, localized clusters displayed a wide range of estimated initial secondary infection rates, for which uniform public health interventions are unlikely to have sustainable effects. Our findings highlight the presence of so-called "super-spreaders", with the propensity to infect a larger-than-average number of people, in countries, such as the USA, for which additional mitigation efforts targeting events surrounding this type of spread are urgently needed to curb further dissemination of SARS-CoV-2.
Keywords	covid19
Language	English
Publishing date	2020-11-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.11.06.370999
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Article ; Online: Evolution of Viral Genomes: Interplay Between Selection, Recombination, and Other Forces.

Spielman, Stephanie J / Weaver, Steven / Shank, Stephen D / Magalis, Brittany Rife / Li, Michael / Kosakovsky Pond, Sergei L

Methods in molecular biology (Clifton, N.J.)

2019 Volume 1910, Page(s) 427–468

Abstract: Natural selection is a fundamental force shaping organismal evolution, as it both maintains function and enables adaptation and innovation. Viruses, with their typically short and largely coding genomes, experience strong and diverse selective forces, ... ...

Abstract	Natural selection is a fundamental force shaping organismal evolution, as it both maintains function and enables adaptation and innovation. Viruses, with their typically short and largely coding genomes, experience strong and diverse selective forces, sometimes acting on timescales that can be directly measured. These selection pressures emerge from an antagonistic interplay between rapidly changing fitness requirements (immune and antiviral responses from hosts, transmission between hosts, or colonization of new host species) and functional imperatives (the ability to infect hosts or host cells and replicate within hosts). Indeed, computational methods to quantify these evolutionary forces using molecular sequence data were initially, dating back to the 1980s, applied to the study of viral pathogens. This preference largely emerged because the strong selective forces are easiest to detect in viruses, and, of course, viruses have clear biomedical relevance. Recent commoditization of affordable high-throughput sequencing has made it possible to generate truly massive genomic data sets, on which powerful and accurate methods can yield a very detailed depiction of when, where, and (sometimes) how viral pathogens respond to various selective forces.Here, we present recent statistical developments and state-of-the-art methods to identify and characterize these selection pressures from protein-coding sequence alignments and phylogenies. Methods described here can reveal critical information about various evolutionary regimes, including whole-gene selection, lineage-specific selection, and site-specific selection acting upon viral genomes, while accounting for confounding biological processes, such as recombination and variation in mutation rates.
MeSH term(s)	Codon ; Computational Biology/methods ; Evolution, Molecular ; Genetic Variation ; Genome, Viral ; Genomics/methods ; Phylogeny ; Recombination, Genetic ; Selection, Genetic ; Software ; Viruses/classification ; Viruses/genetics
Chemical Substances	Codon
Language	English
Publishing date	2019-07-05
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9074-0_14
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Article ; Online: Rapid Emergence and Spread of Severe Acute Respiratory Syndrome Coronavirus 2 Gamma (P.1) Variant in Haiti.

Tagliamonte, Massimiliano S / Mavian, Carla / Zainabadi, Kayvan / Cash, Melanie N / Lednicky, John A / Magalis, Brittany Rife / Riva, Alberto / Deschamps, Marie Marcelle / Liautaud, Bernard / Rouzier, Vanessa / Fitzgerald, Daniel W / Pape, Jean William / Morris, J Glenn / Salemi, Marco

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 74, Issue 11, Page(s) 2057–2060

Abstract: After an initial wave of coronavirus disease 2019 (COVID-19) in Haiti in summer 2020 (primarily lineage B.1), seropositivity for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) was ~40%. Variant P.1 (gamma) was ... ...

Abstract	After an initial wave of coronavirus disease 2019 (COVID-19) in Haiti in summer 2020 (primarily lineage B.1), seropositivity for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) was ~40%. Variant P.1 (gamma) was introduced in February 2021, with an initially limited introduction followed by exponential local dissemination within this unvaccinated population with prior exposure to earlier SARS-CoV-2 lineages.
MeSH term(s)	COVID-19 ; COVID-19 Testing ; Haiti/epidemiology ; Humans ; SARS-CoV-2/genetics
Language	English
Publishing date	2021-08-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab736
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets.

Mavian, Carla / Ramirez-Mata, Andrea S / Dollar, James Jarad / Nolan, David J / Cash, Melanie / White, Kevin / Rich, Shannan N / Magalis, Brittany Rife / Marini, Simone / Prosperi, Mattia C F / Amador, David Moraga / Riva, Alberto / Williams, Kenneth C / Salemi, Marco

Journal of neurovirology

2021 Volume 27, Issue 1, Page(s) 101–115

Abstract: Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals' quality of life, as well as ... ...

Abstract	Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals' quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n = 11), with or without CD8+ lymphocyte depletion, based on detectable (n = 6) or non-detectable (n = 5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction. Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.
MeSH term(s)	Animals ; Cognition Disorders/metabolism ; Cognition Disorders/virology ; Frontal Lobe/metabolism ; Frontal Lobe/virology ; Macaca mulatta ; Male ; Poly(ADP-ribose) Polymerases/metabolism ; Simian Acquired Immunodeficiency Syndrome/metabolism ; Simian Acquired Immunodeficiency Syndrome/virology
Chemical Substances	Poly(ADP-ribose) Polymerases (EC 2.4.2.30)
Language	English
Publishing date	2021-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-020-00927-z
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Zs.A 4426: Show issues

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Article ; Online: HyPhy 2.5-A Customizable Platform for Evolutionary Hypothesis Testing Using Phylogenies.

Kosakovsky Pond, Sergei L / Poon, Art F Y / Velazquez, Ryan / Weaver, Steven / Hepler, N Lance / Murrell, Ben / Shank, Stephen D / Magalis, Brittany Rife / Bouvier, Dave / Nekrutenko, Anton / Wisotsky, Sadie / Spielman, Stephanie J / Frost, Simon D W / Muse, Spencer V

Molecular biology and evolution

2019 Volume 37, Issue 1, Page(s) 295–299

Abstract: HYpothesis testing using PHYlogenies (HyPhy) is a scriptable, open-source package for fitting a broad range of evolutionary models to multiple sequence alignments, and for conducting subsequent parameter estimation and hypothesis testing, primarily in ... ...

Abstract	HYpothesis testing using PHYlogenies (HyPhy) is a scriptable, open-source package for fitting a broad range of evolutionary models to multiple sequence alignments, and for conducting subsequent parameter estimation and hypothesis testing, primarily in the maximum likelihood statistical framework. It has become a popular choice for characterizing various aspects of the evolutionary process: natural selection, evolutionary rates, recombination, and coevolution. The 2.5 release (available from www.hyphy.org) includes a completely re-engineered computational core and analysis library that introduces new classes of evolutionary models and statistical tests, delivers substantial performance and stability enhancements, improves usability, streamlines end-to-end analysis workflows, makes it easier to develop custom analyses, and is mostly backward compatible with previous HyPhy releases.
MeSH term(s)	Genetic Techniques ; Phylogeny ; Software
Language	English
Publishing date	2019-09-10
Publishing country	United States
Document type	Evaluation Study ; Journal Article
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msz197
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Article ; Online: SARS-CoV-2 Delta vaccine breakthrough transmissibility in Alachua, Florida

medRxiv

Abstract: Background SARS-CoV-2 Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals. Methods Between October 2020 and July 2021, we sequenced 4,439 ... ...

Abstract	Background SARS-CoV-2 Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals. Methods Between October 2020 and July 2021, we sequenced 4,439 SARS-CoV-2 full genomes, 23% of all known infections in Alachua County, Florida, including 109 vaccine breakthrough cases. Univariate and multivariate regression analyses were conducted to evaluate associations between viral load (VL) level and patient characteristics. Contact tracing and phylogenetic analysis were used to investigate direct transmissions involving vaccinated individuals. Results The majority of breakthrough sequences with lineage assignment were classified as Delta variants (74.6%) and occurred, on average, about three months (104 +- 57.5 days) after full vaccination, at the same time (June-July 2021) of Delta variant exponential spread within the county. Six Delta variant transmission pairs between fully vaccinated individuals were identified through contact tracing, three of which were confirmed by phylogenetic analysis. Delta breakthroughs exhibited broad VL values during acute infection (IQR 1.2-8.64 Log copies/ml), on average 38% lower than matched unvaccinated patients (3.29-10.81 Log copies/ml, p<0.00001). Nevertheless, 49-50% of all breakthroughs, and 56-60% of Delta-infected breakthroughs exhibited VL above the transmissibility threshold (4 Log copies/ml) irrespective of time post vaccination. Conclusions Delta infection transmissibility and general VL patterns in vaccinated individuals suggest limited levels of sterilizing immunity that need to be considered by public health policies. In particular, ongoing evaluation of vaccine boosters should address whether extra vaccine doses might curb breakthrough contribution to epidemic spread.
Keywords	covid19
Language	English
Publishing date	2021-11-11
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.11.10.21266134
Database	COVID19

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