Rapid, efficient differential diagnosis is critical to controlling the morbidity and mortality of acute infectious diseases and to enabling efficient resource allocation. Many infectious diseases present with non-specific signs and symptoms;hence, history and physical exam alone are typically insufficient to inform clinical management or characterize outbreaks. A wide range of molecular methods have been developed for direct detection of microbial nucleic acids in clinical materials. These advances have transformed microbiology and medicine;nonetheless, high throughput sequencing, the most highly multiplexed of these methods, remains too complex and expensive for application in many clinical settings. Furthermore, none of these methods will serve in instances where microbial nucleic acids are not present in an accessible sample or where disease may have been triggered by an agent that is no longer present. The risk of developing disease and its severity after exposure to an infectious agent is modulated by an individual's previous exposures to similar agents or vaccines. Such exposures may confer complete or partial protection or result in increased risk for more severe disease due to antibody-mediated enhancement, as is the case in dengue fever. Thus, knowledge of an individual's immunological history may influence decisions concerning his/her treatment, vaccination or deployment as a first responder or health care worker in areas with increased probability of encountering specific pathogens. Our objective is to enhance differential diagnosis and management of infectious diseases through pursuit of two aims that will (1) establish a new highly multiplexed serology platform for profiling a subject's pathogen exposure history and (2) improve the efficiency of sequencing for direct detection of microbial nucleic acids in clinical specimens. Investments in sequencing have largely focused on driving down costs per base and on increasing read length and number. We will complement these efforts by establishing new methods for sample preparation that will enrich for relevant template, thereby enhancing efficiency and reducing the complexity of bioinformatic analyses.

Public Health Relevance

This project will reduce the morbidity, mortality and economic cost of infectious diseases by providing new tools for diagnosis and discovery of infectious agents, as well as detecting evidence of exposure.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-LR-M (J1))
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Columbia University
New York
United States
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Lindow, Janet C; Wunder Jr, Elsio A; Popper, Stephen J et al. (2016) Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLoS Pathog 12:e1005943
Bouilly, Delphine; Hon, Jason; Daly, Nathan S et al. (2016) Single-Molecule Reaction Chemistry in Patterned Nanowells. Nano Lett 16:4679-85
Bacharach, Eran; Mishra, Nischay; Briese, Thomas et al. (2016) Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of Tilapia. MBio 7:e00431-16
Beall, Anne; Yount, Boyd; Lin, Chun-Ming et al. (2016) Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A. MBio 7:e01451-15
Forero, Adriana; Tisoncik-Go, Jennifer; Watanabe, Tokiko et al. (2016) The 1918 Influenza Virus PB2 Protein Enhances Virulence through the Disruption of Inflammatory and Wnt-Mediated Signaling in Mice. J Virol 90:2240-53
Tisoncik-Go, Jennifer; Gasper, David J; Kyle, Jennifer E et al. (2016) Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism. Cell Host Microbe 19:254-66
Warren, Steven B; Vernick, Sefi; Romano, Ethan et al. (2016) Complementary Metal-Oxide-Semiconductor Integrated Carbon Nanotube Arrays: Toward Wide-Bandwidth Single-Molecule Sensing Systems. Nano Lett 16:2674-9
Strouts, Fiona R; Popper, Stephen J; Partidos, Charalambos D et al. (2016) Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates. PLoS Negl Trop Dis 10:e0004731
Menachery, Vineet D; Yount Jr, Boyd L; Sims, Amy C et al. (2016) SARS-like WIV1-CoV poised for human emergence. Proc Natl Acad Sci U S A 113:3048-53
Tokarz, Rafal; Sameroff, Stephen; Hesse, Richard A et al. (2015) Discovery of a novel nidovirus in cattle with respiratory disease. J Gen Virol 96:2188-93

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