The Bioinformatics and Biostatistics Core will provide systems and bioinformatics computing infrastructure necessary for tracking, storing, integrating, and biostatistical analysis of the data generated in Research Projects 1-3. To accomplish this we will implement a custom database that supports the storage and organization of the immunological data, patient phenotypes, test results, 'omics data, SOPs, and other resources generated by this project. The system will be based on the Open Science Data Framework (OSDF), a scalable file system that will accommodate all information specific to this U19. We will also scale up our high-capacity data storage infrastructure to store, manage, and share these data. The proposed experiments in the Research Projects are complex, often involving clustered and longitudinal data, and correlated predictors and to appropriately assess the evidence in the data advanced statistical methods will be utilized. We will provide biostatistics expertise for design of experiments and ensure that they are unconfounded, optimally efficient, and appropriately powered. The Core biostatistics experts will help investigators summarize, analyze, interpret, and present the results. Finally, we will provide rapid data release and dissemination to the scientific community. Primary data such as sequence will be deposited in public archives such as the NCBI Short Read Archive (SRA), and the derived results such as genome assemblies, sequence variants, and expression data in NCBI Genbank, dbSNP, and the Gene Expression Omnibus (GEO). In addition to deposition of data to public archives, we will build a website for the scientific community to access all raw and custom data sets, analysis tools and standard operating procedure documents.

Public Health Relevance

The Bioinformatics and Biostatistics Core will provide systems and bioinformatics computing infrastructure necessary for tracking, storing, integrating, and biostatistical analysis of the data generated in Research Projects 1-3. To accomplish this we will implement a custom database that supports the storage and organization of the immunological data, patient phenotypes, test results, 'omics data, SOPs, and other resources generated by this project. The system will be based on the Open Science Data Framework (OSDF), a scalable file system that will accommodate all information specific to this U19. We will also scale up our high-capacity data storage infrastructure to store, manage, and share these data. The proposed experiments in the Research Projects are complex, often involving clustered and longitudinal data, and correlated predictors and to appropriately assess the evidence in the data advanced statistical methods will be utilized. We will provide biostatistics expertise for design of experiments and ensure that they are unconfounded, optimally efficient, and appropriately powered. The Core biostatistics experts will help investigators summarize, analyze, interpret, and present the results. Finally, we will provide rapid data release and dissemination to the scientific community. Primary data such as sequence will be deposited in public archives such as the NCBI Short Read Archive (SRA), and the derived results such as genome assemblies, sequence variants, and expression data in NCBI Genbank, dbSNP, and the Gene Expression Omnibus (GEO). In addition to deposition of data to public archives, we will build a website for the scientific community to access all raw and custom data sets, analysis tools and standard operating procedure documents. This Bioinformatics and Biostatistical Core will provide the infrastructure for computational storage, as well as data processing, and data integration and statistical analysis required for this project. This core will be critical in understanding the interplay human immune response and the gut microbiota and the consequences of the initial S. Typhi-human intestinal mucosa interactions on innate immunity and gut physiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19AI082655-06
Application #
8726152
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Salerno-Goncalves, R; Safavie, F; Fasano, A et al. (2016) Free and complexed-secretory immunoglobulin A triggers distinct intestinal epithelial cell responses. Clin Exp Immunol 185:338-47
Fresnay, Stephanie; McArthur, Monica A; Magder, Laurence et al. (2016) Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans. J Transl Med 14:62
Blohmke, Christoph J; Darton, Thomas C; Jones, Claire et al. (2016) Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever. J Exp Med 213:1061-77
Salerno-Goncalves, Rosangela; Fasano, Alessio; Sztein, Marcelo B (2016) Development of a Multicellular Three-dimensional Organotypic Model of the Human Intestinal Mucosa Grown Under Microgravity. J Vis Exp :
McArthur, Monica A; Fresnay, Stephanie; Magder, Laurence S et al. (2015) Activation of Salmonella Typhi-specific regulatory T cells in typhoid disease in a wild-type S. Typhi challenge model. PLoS Pathog 11:e1004914
Trebicka, Estela; Shanmugam, Nanda Kumar N; Chen, Kejie et al. (2015) Intestinal Inflammation Leads to a Long-lasting Increase in Resistance to Systemic Salmonellosis that Requires Macrophages But Not B or T Lymphocytes at the Time of Pathogen Challenge. Inflamm Bowel Dis 21:2758-65
Wahid, R; Fresnay, S; Levine, M M et al. (2015) Immunization with Ty21a live oral typhoid vaccine elicits crossreactive multifunctional CD8+ T-cell responses against Salmonella enterica serovar Typhi, S. Paratyphi A, and S. Paratyphi B in humans. Mucosal Immunol 8:1349-59
Booth, Jayaum S; Salerno-Goncalves, Rosangela; Blanchard, Thomas G et al. (2015) Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection. Front Immunol 6:466
Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie et al. (2015) Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease. PLoS Negl Trop Dis 9:e0003837
Sztein, Marcelo B; Salerno-Goncalves, Rosangela; McArthur, Monica A (2014) Complex adaptive immunity to enteric fevers in humans: lessons learned and the path forward. Front Immunol 5:516

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