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Showing papers by "Bruce W. Birren published in 2014"


Journal ArticleDOI
12 Sep 2014-Science
TL;DR: This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources.
Abstract: In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.

1,164 citations


Journal ArticleDOI
17 Jul 2014-Cell
TL;DR: A novel algorithm is used to systematically identify BGCs in the extensive extant microbial sequencing data, indicating for the first time the important roles these compounds play in Gram-negative cell biology.

720 citations


Journal ArticleDOI
TL;DR: A robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples using targeted RNase H-based digestion and a hybrid-selection protocol to further enrich the viral content of sequencing libraries.
Abstract: We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies.

135 citations


Journal ArticleDOI
TL;DR: It is shown that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.
Abstract: The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

108 citations


Journal ArticleDOI
31 Dec 2014-Mbio
TL;DR: In the largest and most comprehensive comparison of sequenced Fusobacterium species to date, this study generates a testable model for the molecular pathogenesis of FusOBacterium infection and illuminate new therapeutic or diagnostic strategies.
Abstract: The diverseFusobacterium genus contains species implicated in multiple clinical pathologies, including periodontal disease, preterm birth, and colorectal cancer. The lack of genetic tools for manipulating these organisms leaves us with little un- derstanding of the genes responsible for adherence to and invasion of host cells. Actively invading Fusobacterium species can enter host cells independently, whereas passively invading species need additional factors, such as compromise of mucosal integ- rity or coinfection with other microbes. We applied whole-genome sequencing and comparative analysis to study the evolution of active and passive invasion strategies and to infer factors associated with active forms of host cell invasion. The evolution of active invasion appears to have followed an adaptive radiation in which two of the three fusobacterial lineages acquired new genes and underwent expansions of ancestral genes that enable active forms of host cell invasion. Compared to passive invaders, active invaders have much larger genomes, encode FadA-related adhesins, and possess twice as many genes encoding membrane- related proteins, including a large expansion of surface-associated proteins containing the MORN2 domain of unknown func- tion. We predict a role for proteins containing MORN2 domains in adhesion and active invasion. In the largest and most com- prehensive comparison of sequenced Fusobacterium species to date, we have generated a testable model for the molecular pathogenesis ofFusobacterium infection and illuminate new therapeutic or diagnostic strategies. IMPORTANCE Fusobacterium species have recently been implicated in a broad spectrum of human pathologies, including Crohn's disease, ulcerative colitis, preterm birth, and colorectal cancer. Largely due to the genetic intractability of member species, the mechanisms by which Fusobacterium causes these pathologies are not well understood, although adherence to and active inva- sion of host cells appear important. We examined whole-genome sequence data from a diverse set of Fusobacterium species to identify genetic determinants of active forms of host cell invasion. Our analyses revealed that actively invading Fusobacterium species have larger genomes than passively invading species and possess a specific complement of genes—including a class of genes of unknown function that we predict evolved to enable host cell adherence and invasion. This study provides an important framework for future studies on the role of Fusobacterium in pathologies such as colorectal cancer.

85 citations


Journal ArticleDOI
17 Jun 2014-PLOS ONE
TL;DR: The use of this metadata standard by all ongoing and future GSCID sequencing projects will provide a consistent representation of these data in the BRC resources and other repositories that leverage these data, allowing investigators to identify relevant genomic sequences and perform comparative genomics analyses that are both statistically meaningful and biologically relevant.
Abstract: High throughput sequencing has accelerated the determination of genome sequences for thousands of human infectious disease pathogens and dozens of their vectors. The scale and scope of these data are enabling genotype-phenotype association studies to identify genetic determinants of pathogen virulence and drug/insecticide resistance, and phylogenetic studies to track the origin and spread of disease outbreaks. To maximize the utility of genomic sequences for these purposes, it is essential that metadata about the pathogen/vector isolate characteristics be collected and made available in organized, clear, and consistent formats. Here we report the development of the GSCID/BRC Project and Sample Application Standard, developed by representatives of the Genome Sequencing Centers for Infectious Diseases (GSCIDs), the Bioinformatics Resource Centers (BRCs) for Infectious Diseases, and the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), informed by interactions with numerous collaborating scientists. It includes mapping to terms from other data standards initiatives, including the Genomic Standards Consortium’s minimal information (MIxS) and NCBI’s BioSample/BioProjects checklists and the Ontology for Biomedical Investigations (OBI). The standard includes data fields about characteristics of the organism or environmental source of the specimen, spatial-temporal information about the specimen isolation event, phenotypic characteristics of the pathogen/vector isolated, and project leadership and support. By modeling metadata fields into an ontology-based semantic framework and reusing existing ontologies and minimum information checklists, the application standard can be extended to support additional project-specific data fields and integrated with other data represented with comparable standards. The use of this metadata standard by all ongoing and future GSCID sequencing projects will provide a consistent representation of these data in the BRC resources and other repositories that leverage these data, allowing investigators to identify relevant genomic sequences and perform comparative genomics analyses that are both statistically meaningful and biologically relevant.

35 citations


Journal ArticleDOI
TL;DR: The genome sequence of S. scenckii is reported, which will facilitate the study of this fungus and of the Sporothrix schenckii group.
Abstract: Sporothrix schenckii is a pathogenic dimorphic fungus that grows as a yeast and as mycelia. This species is the causative agent of sporotrichosis, typically a skin infection. We report the genome sequence of S. schenckii, which will facilitate the study of this fungus and of the Sporothrix schenckii group.

32 citations


Journal ArticleDOI
TL;DR: The data suggest that gene-targeted metagenomic analysis is useful for an in-depth understanding of the diversity of a particular gene of interest and specific carbohydrate metabolic genes appear to be carried by distinct OTUs in different individual hosts and among different vertebrate species’ microbiomes.
Abstract: Glycoside hydrolases (GHs), the enzymes that breakdown complex carbohydrates, are a highly diversified class of key enzymes associated with the gut microbiota and its metabolic functions To learn more about the diversity of GHs and their potential role in a variety of gut microbiomes, we used a combination of 16S, metagenomic and targeted amplicon sequencing data to study one of these enzyme families in detail Specifically, we employed a functional gene-targeted metagenomic approach to the 1-4-α-glucan-branching enzyme (gBE) gene in the gut microbiomes of four host species (human, chicken, cow and pig) The characteristics of operational taxonomic units (OTUs) and operational glucan-branching units (OGBUs) were distinctive in each of hosts Human and pig were most similar in OTUs profiles while maintaining distinct OGBU profiles Interestingly, the phylogenetic profiles identified from 16S and gBE gene sequences differed, suggesting the presence of different gBE genes in the same OTU across different vertebrate hosts Our data suggest that gene-targeted metagenomic analysis is useful for an in-depth understanding of the diversity of a particular gene of interest Specific carbohydrate metabolic genes appear to be carried by distinct OTUs in different individual hosts and among different vertebrate species' microbiomes, the characteristics of which differ according to host genetic background and/or diet

30 citations


Journal ArticleDOI
07 Aug 2014-PLOS ONE
TL;DR: It is found that the Winogradsky columns were highly diverse communities but are dominated by three phyla: Proteobacteria, Bacteroidetes, and Firmicutes, showing that different taxonomic groups carry out sulfur cycling in different columns.
Abstract: A Winogradsky column is a clear glass or plastic column filled with enriched sediment. Over time, microbial communities in the sediment grow in a stratified ecosystem with an oxic top layer and anoxic sub-surface layers. Winogradsky columns have been used extensively to demonstrate microbial nutrient cycling and metabolic diversity in undergraduate microbiology labs. In this study, we used high-throughput 16s rRNA gene sequencing to investigate the microbial diversity of Winogradsky columns. Specifically, we tested the impact of sediment source, supplemental cellulose source, and depth within the column, on microbial community structure. We found that the Winogradsky columns were highly diverse communities but are dominated by three phyla: Proteobacteria, Bacteroidetes, and Firmicutes. The community is structured by a founding population dependent on the source of sediment used to prepare the columns and is differentiated by depth within the column. Numerous biomarkers were identified distinguishing sample depth, including Cyanobacteria, Alphaproteobacteria, and Betaproteobacteria as biomarkers of the soil-water interface, and Clostridia as a biomarker of the deepest depth. Supplemental cellulose source impacted community structure but less strongly than depth and sediment source. In columns dominated by Firmicutes, the family Peptococcaceae was the most abundant sulfate reducer, while in columns abundant in Proteobacteria, several Deltaproteobacteria families, including Desulfobacteraceae, were found, showing that different taxonomic groups carry out sulfur cycling in different columns. This study brings this historical method for enrichment culture of chemolithotrophs and other soil bacteria into the modern era of microbiology and demonstrates the potential of the Winogradsky column as a model system for investigating the effect of environmental variables on soil microbial communities.

30 citations


Journal ArticleDOI
TL;DR: In this article, the authors looked at combined host and pathogen factors in a prospective cohort and found that MRSA carriage in the United States is at least 7% in general hospital populations and as high as 24% in intensive care units (ICUs).
Abstract: (See the editorial commentary by Stevenson and Wang on pages 488–90.) Staphylococcus aureus is a major cause of healthcare-associated infections [1], and patients are often colonized with this bacterium before developing invasive disease [2, 3]. Increasing carriage of methicillin-resistant S. aureus (MRSA), an antibiotic-resistant strain, has resulted in a doubling of MRSA-related hospitalizations, including up to 56 000 US hospitalizations per year for MRSA bacteremia [4–6]. Overall, nearly 19 000 patients die annually in US hospitals from MRSA infections [7]. MRSA carriage in the United States is at least 7% in general hospital populations [8] and as high as 24% in intensive care units (ICUs) [9]. The risk of MRSA infection in the year following colonization is as high as 33%, with 18% being primary bloodstream infections [10]. Nasal carriers of MRSA versus methicillin-susceptible S. aureus (MSSA) have a 4 times higher incidence of bacteremia, with >80% of cases involving an identical strain in the nares and the blood [3, 11, 12]. In addition, the mortality for bacteremia is 2 times higher with MRSA as compared to MSSA [13]. Both host and pathogen factors play a role in the development of MRSA infections. Host factors include prolonged hospitalization [14–17], advanced age [10, 14], intravenous catheterization [15, 17–19], mechanical ventilation [18, 20, 21], antibiotic exposure [17, 21], soft-tissue wounds [15, 19], and chronic diseases, such as diabetes, renal insufficiency, cancer, and malnutrition [10, 18, 22]. Pathogen factors predicting MRSA bacteremia are the subject of ongoing debate [23]. Studies accounting for epidemiologic factors of the host in addition to genetic variation in different MRSA strains are lacking. We therefore sought to look at combined host and pathogen factors in a prospective cohort.

28 citations