Publications by authors named "Anderson F Brito"

11 Publications

  • Page 1 of 1

Early introductions and community transmission of SARS-CoV-2 variant B.1.1.7 in the United States.

medRxiv 2021 Feb 12. Epub 2021 Feb 12.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a national public health concern in the United States because of its increased transmissibility. Over 500 COVID-19 cases associated with this variant have been detected since December 2020, but its local establishment and pathways of spread are relatively unknown. Using travel, genomic, and diagnostic testing data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. New York, which receives the most international travel from the UK, is likely one of the key hubs for introductions and domestic spread. Finally, we provide evidence for increased community transmission in several states. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.02.10.21251540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885932PMC
February 2021

NCBI's Virus Discovery Codeathon: Building "FIVE" -The Federated Index of Viral Experiments API Index.

Viruses 2020 12 10;12(12). Epub 2020 Dec 10.

National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20894, USA.

Viruses represent important test cases for data federation due to their genome size and the rapid increase in sequence data in publicly available databases. However, some consequences of previously decentralized (unfederated) data are lack of consensus or comparisons between feature annotations. Unifying or displaying alternative annotations should be a priority both for communities with robust entry representation and for nascent communities with burgeoning data sources. To this end, during this three-day continuation of the Virus Hunting Toolkit codeathon series (VHT-2), a new integrated and federated viral index was elaborated. This Federated Index of Viral Experiments (FIVE) integrates pre-existing and novel functional and taxonomy annotations and virus-host pairings. Variability in the context of viral genomic diversity is often overlooked in virus databases. As a proof-of-concept, FIVE was the first attempt to include viral genome variation for HIV, the most well-studied human pathogen, through viral genome diversity graphs. As per the publication of this manuscript, FIVE is the first implementation of a virus-specific federated index of such scope. FIVE is coded in BigQuery for optimal access of large quantities of data and is publicly accessible. Many projects of database or index federation fail to provide easier alternatives to access or query information. To this end, a Python API query system was developed to enhance the accessibility of FIVE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12121424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764237PMC
December 2020

Real-time public health communication of local SARS-CoV-2 genomic epidemiology.

PLoS Biol 2020 08 21;18(8):e3000869. Epub 2020 Aug 21.

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.

Genomic epidemiology can provide a unique, real-time understanding of SARS-CoV-2 transmission patterns. Yet the potential for genomic analyses to guide local policy and community-based behavioral decisions is limited because they are often oriented towards specially trained scientists and conducted on a national or global scale. Here, we propose a new paradigm: Phylogenetic analyses performed on a local level (municipal, county, or state), with results communicated in a clear, timely, and actionable manner to strengthen public health responses. We believe that presenting results rapidly, and tailored to a non-expert audience, can serve as a template for effective public health response to COVID-19 and other emerging viral diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.3000869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467297PMC
August 2020

Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT-qPCR primer-probe sets.

Nat Microbiol 2020 10 10;5(10):1299-1305. Epub 2020 Jul 10.

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.

The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for accurate and rapid diagnostic assays to prompt clinical and public health interventions. Currently, several quantitative reverse transcription-PCR (RT-qPCR) assays are being used by clinical, research and public health laboratories. However, it is currently unclear whether results from different tests are comparable. Our goal was to make independent evaluations of primer-probe sets used in four common SARS-CoV-2 diagnostic assays. From our comparisons of RT-qPCR analytical efficiency and sensitivity, we show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 viral RNA copies per reaction. The exception for this is the RdRp-SARSr (Charité) confirmatory primer-probe set which has low sensitivity, probably due to a mismatch to circulating SARS-CoV-2 in the reverse primer. We did not find evidence for background amplification with pre-COVID-19 samples or recent SARS-CoV-2 evolution decreasing sensitivity. Our recommendation for SARS-CoV-2 diagnostic testing is to select an assay with high sensitivity and that is regionally used, to ease comparability between outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-020-0761-6DOI Listing
October 2020

Host response-based screening to identify undiagnosed cases of COVID-19 and expand testing capacity.

medRxiv 2020 Jun 5. Epub 2020 Jun 5.

The COVID-19 pandemic has created unprecedented challenges in diagnostic testing. At the beginning of the epidemic, a confluence of factors resulted in delayed deployment of PCR-based diagnostic tests, resulting in lack of testing of individuals with symptoms of the disease. Although these tests are now more widely available, it is estimated that a three- to ten-fold increase in testing capacity will be required to ensure adequate surveillance as communities reopen(1). In response to these challenges, we evaluated potential roles of host-response based screening in the diagnosis of COVID-19. Previous work from our group showed that the nasopharyngeal (NP) level of CXCL10, a protein produced as part of the host response to viral infection, is a sensitive predictor of respiratory virus infection across a wide spectrum of viruses(2). Here, we show that NP CXCL10 is elevated during SARS-CoV-2 infection and use a CXCL10-based screening strategy to identify four undiagnosed cases of COVID-19 in Connecticut in early March. In a second set of samples tested at the Yale New Haven Hospital, we show that NP CXCL10 had excellent performance as a rule-out test (NPV 0.99, 95% C.I. 0.985-0.997). Our results demonstrate how biomarker-based screening could be used to leverage existing PCR testing capacity to rapidly enable widespread testing for COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2020.06.04.20109306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302303PMC
June 2020

SARS-CoV-2 infection of the placenta.

J Clin Invest 2020 09;130(9):4947-4953

Department of Obstetrics, Gynecology, and Reproductive Sciences.

BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI139569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456249PMC
September 2020

Coast-to-coast spread of SARS-CoV-2 in the United States revealed by genomic epidemiology.

medRxiv 2020 Mar 26. Epub 2020 Mar 26.

Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2020.03.25.20043828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276058PMC
March 2020

Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States.

Cell 2020 05 7;181(5):990-996.e5. Epub 2020 May 7.

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA. Electronic address:

The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204677PMC
May 2020

The evolution of protein domain repertoires: Shedding light on the origins of the family.

Virus Evol 2020 Jan 5;6(1):veaa001. Epub 2020 Feb 5.

Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

Herpesviruses (HVs, Family: ) have large genomes that encode hundreds of proteins. Apart from amino acid mutations, protein domain acquisitions, duplications and losses are also common modes of evolution. HV domain repertoires differ across species, and only a core set is shared among all species, aspect that raises a question: How have HV domain repertoires diverged while keeping some similarities? To answer such question, we used profile Hidden Markov Models (HMMs) to search for domains in all possible translated open reading frames (ORFs) of fully sequenced HV genomes. With at least 274 domains being identified, we built a matrix of domain counts per species, and applied a parsimony method to reconstruct the ancestral states of these domains along the HV phylogeny. It revealed events of domain gain, duplication, and loss over more than 400 millions of years, where Alpha-, Beta-, and GammaHVs expanded and condensed their domain repertoires at distinct rates. Most of the acquired domains perform 'Modulation and Control', 'Envelope', or 'Auxiliary' functions, categories that showed high flexibility (number of domains) and redundancy (number of copies). Conversely, few gains and duplications were observed for domains involved in 'Capsid assembly and structure', and 'DNA Replication, recombination and metabolism'. Among the forty-one primordial domains encoded by ancestors, twenty-eight are still found in all present-day HVs. Because of their distinct evolutionary strategies, HV domain repertoires are very specific at the subfamily, genus and species levels. Differences in domain composition may not only explain HV host range and tissue tropism, but also provide hints to the origins of HVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ve/veaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000910PMC
January 2020

Twenty years of West Nile virus spread and evolution in the Americas visualized by Nextstrain.

PLoS Pathog 2019 10 31;15(10):e1008042. Epub 2019 Oct 31.

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.

It has been 20 years since West Nile virus first emerged in the Americas, and since then, little progress has been made to control outbreaks caused by this virus. After its first detection in New York in 1999, West Nile virus quickly spread across the continent, causing an epidemic of human disease and massive bird die-offs. Now the virus has become endemic to the United States, where an estimated 7 million human infections have occurred, making it the leading mosquito-borne virus infection and the most common cause of viral encephalitis in the country. To bring new attention to one of the most important mosquito-borne viruses in the Americas, we provide an interactive review using Nextstrain: a visualization tool for real-time tracking of pathogen evolution (nextstrain.org/WNV/NA). Nextstrain utilizes a growing database of more than 2,000 West Nile virus genomes and harnesses the power of phylogenetics for students, educators, public health workers, and researchers to visualize key aspects of virus spread and evolution. Using Nextstrain, we use virus genomics to investigate the emergence of West Nile virus in the U S, followed by its rapid spread, evolution in a new environment, establishment of endemic transmission, and subsequent international spread. For each figure, we include a link to Nextstrain to allow the readers to directly interact with and explore the underlying data in new ways. We also provide a brief online narrative that parallels this review to further explain the data and highlight key epidemiological and evolutionary features (nextstrain.org/narratives/twenty-years-of-WNV). Mirroring the dynamic nature of outbreaks, the Nextstrain links provided within this paper are constantly updated as new West Nile virus genomes are shared publicly, helping to stay current with the research. Overall, our review showcases how genomics can track West Nile virus spread and evolution, as well as potentially uncover novel targeted control measures to help alleviate its public health burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1008042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822705PMC
October 2019

Protein-Protein Interactions in Virus-Host Systems.

Front Microbiol 2017 17;8:1557. Epub 2017 Aug 17.

Department of Life Sciences, Centre for Integrative Systems Biology and Bioinformatics, Imperial College LondonLondon, United Kingdom.

To study virus-host protein interactions, knowledge about viral and host protein architectures and repertoires, their particular evolutionary mechanisms, and information on relevant sources of biological data is essential. The purpose of this review article is to provide a thorough overview about these aspects. Protein domains are basic units defining protein interactions, and the uniqueness of viral domain repertoires, their mode of evolution, and their roles during viral infection make viruses interesting models of study. Mutations at protein interfaces can reduce or increase their binding affinities by changing protein electrostatics and structural properties. During the course of a viral infection, both pathogen and cellular proteins are constantly competing for binding partners. Endogenous interfaces mediating intraspecific interactions-viral-viral or host-host interactions-are constantly targeted and inhibited by exogenous interfaces mediating viral-host interactions. From a biomedical perspective, blocking such interactions is the main mechanism underlying antiviral therapies. Some proteins are able to bind multiple partners, and their modes of interaction define how fast these "hub proteins" evolve. "Party hubs" have multiple interfaces; they establish simultaneous/stable (domain-domain) interactions, and tend to evolve slowly. On the other hand, "date hubs" have few interfaces; they establish transient/weak (domain-motif) interactions by means of short linear peptides (15 or fewer residues), and can evolve faster. Viral infections are mediated by several protein-protein interactions (PPIs), which can be represented as networks (protein interaction networks, PINs), with proteins being depicted as nodes, and their interactions as edges. It has been suggested that viral proteins tend to establish interactions with more central and highly connected host proteins. In an evolutionary arms race, viral and host proteins are constantly changing their interface residues, either to evade or to optimize their binding capabilities. Apart from gaining and losing interactions via rewiring mechanisms, virus-host PINs also evolve via gene duplication (paralogy); conservation (orthology); horizontal gene transfer (HGT) (xenology); and molecular mimicry (convergence). The last sections of this review focus on PPI experimental approaches and their limitations, and provide an overview of sources of biomolecular data for studying virus-host protein interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2017.01557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562681PMC
August 2017