Browsing by Author "Ternus, Krista L."

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    Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease
    (Springer Nature, 2022) Jochum, Michael; Lee, Michael D.; Curry, Kristen; Zaksas, Victoria; Vitalis, Elizabeth; Treangen, Todd; Aagaard, Kjersti; Ternus, Krista L.
    To better understand the potential relationship between COVID-19 disease and hologenome microbial community dynamics and functional profiles, we conducted a multivariate taxonomic and functional microbiome comparison of publicly available human bronchoalveolar lavage fluid (BALF) metatranscriptome samples amongst COVID-19 (n = 32), community acquired pneumonia (CAP) (n = 25), and uninfected samples (n = 29). We then performed a stratified analysis based on mortality amongst the COVID-19 cohort with known outcomes of deceased (n = 10) versus survived (n = 15). Our overarching hypothesis was that there are detectable and functionally significant relationships between BALF microbial metatranscriptomes and the severity of COVID-19 disease onset and progression. We observed 34 functionally discriminant gene ontology (GO) terms in COVID-19 disease compared to the CAP and uninfected cohorts, and 21 GO terms functionally discriminant to COVID-19 mortality (q < 0.05). GO terms enriched in the COVID-19 disease cohort included hydrolase activity, and significant GO terms under the parental terms of biological regulation, viral process, and interspecies interaction between organisms. Notable GO terms associated with COVID-19 mortality included nucleobase-containing compound biosynthetic process, organonitrogen compound catabolic process, pyrimidine-containing compound biosynthetic process, and DNA recombination, RNA binding, magnesium and zinc ion binding, oxidoreductase activity, and endopeptidase activity. A Dirichlet multinomial mixtures clustering analysis resulted in a best model fit using three distinct clusters that were significantly associated with COVID-19 disease and mortality. We additionally observed discriminant taxonomic differences associated with COVID-19 disease and mortality in the genus Sphingomonas, belonging to the Sphingomonadacae family, Variovorax, belonging to the Comamonadaceae family, and in the class Bacteroidia, belonging to the order Bacteroidales. To our knowledge, this is the first study to evaluate significant differences in taxonomic and functional signatures between BALF metatranscriptomes from COVID-19, CAP, and uninfected cohorts, as well as associating these taxa and microbial gene functions with COVID-19 mortality. Collectively, while this data does not speak to causality nor directionality of the association, it does demonstrate a significant relationship between the human microbiome and COVID-19. The results from this study have rendered testable hypotheses that warrant further investigation to better understand the causality and directionality of host–microbiome–pathogen interactions.
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    Current progress and future opportunities in applications of bioinformatics for biodefense and pathogen detection: report from the Winter Mid-Atlantic Microbiome Meet-up, College Park, MD, January 10, 2018
    (BioMed Central, 2018-11-05) Meisel, Jacquelyn S.; Nasko, Daniel J.; Brubach, Brian; Cepeda-Espinoza, Victoria; Chopyk, Jessica; Corrada-Bravo, Héctor; Fedarko, Marcus; Ghurye, Jay; Javkar, Kiran; Olson, Nathan D.; Shah, Nidhi; Allard, Sarah M.; Bazinet, Adam L.; Bergman, Nicholas H.; Brown, Alexis; Caporaso, J.G.; Conlan, Sean; DiRuggiero, Jocelyne; Forry, Samuel P.; Hasan, Nur A.; Kralj, Jason; Luethy, Paul M.; Milton, Donald K.; Ondov, Brian D.; Preheim, Sarah; Ratnayake, Shashikala; Rogers, Stephanie M.; Rosovitz, M.J.; Sakowski, Eric G.; Schliebs, Nils O.; Sommer, Daniel D.; Ternus, Krista L.; Uritskiy, Gherman; Zhang, Sean X.; Pop, Mihai; Treangen, Todd J.
    Abstract The Mid-Atlantic Microbiome Meet-up (M3) organization brings together academic, government, and industry groups to share ideas and develop best practices for microbiome research. In January of 2018, M3 held its fourth meeting, which focused on recent advances in biodefense, specifically those relating to infectious disease, and the use of metagenomic methods for pathogen detection. Presentations highlighted the utility of next-generation sequencing technologies for identifying and tracking microbial community members across space and time. However, they also stressed the current limitations of genomic approaches for biodefense, including insufficient sensitivity to detect low-abundance pathogens and the inability to quantify viable organisms. Participants discussed ways in which the community can improve software usability and shared new computational tools for metagenomic processing, assembly, annotation, and visualization. Looking to the future, they identified the need for better bioinformatics toolkits for longitudinal analyses, improved sample processing approaches for characterizing viruses and fungi, and more consistent maintenance of database resources. Finally, they addressed the necessity of improving data standards to incentivize data sharing. Here, we summarize the presentations and discussions from the meeting, identifying the areas where microbiome analyses have improved our ability to detect and manage biological threats and infectious disease, as well as gaps of knowledge in the field that require future funding and focus.
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    Improved understanding of biorisk for research involving microbial modification using annotated sequences of concern
    (Frontiers Media S.A., 2023) Godbold, Gene D.; Hewitt, F. Curtis; Kappell, Anthony D.; Scholz, Matthew B.; Agar, Stacy L.; Treangen, Todd J.; Ternus, Krista L.; Sandbrink, Jonas B.; Koblentz, Gregory D.
    Regulation of research on microbes that cause disease in humans has historically been focused on taxonomic lists of ‘bad bugs’. However, given our increased knowledge of these pathogens through inexpensive genome sequencing, 5 decades of research in microbial pathogenesis, and the burgeoning capacity of synthetic biologists, the limitations of this approach are apparent. With heightened scientific and public attention focused on biosafety and biosecurity, and an ongoing review by US authorities of dual-use research oversight, this article proposes the incorporation of sequences of concern (SoCs) into the biorisk management regime governing genetic engineering of pathogens. SoCs enable pathogenesis in all microbes infecting hosts that are ‘of concern’ to human civilization. Here we review the functions of SoCs (FunSoCs) and discuss how they might bring clarity to potentially problematic research outcomes involving infectious agents. We believe that annotation of SoCs with FunSoCs has the potential to improve the likelihood that dual use research of concern is recognized by both scientists and regulators before it occurs.