Abstract
The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten potential diagnostic targets from Bacillus anthracis. The integrative analysis across data sets from multiple centers can reveal potential functional significance and hidden relationships between pathogen and host proteins, thereby providing a systems approach to basic understanding of pathogenicity and target identification.
Highlights
The NIAID (National Institute of Allergy and Infectious Diseases) Biodefense Proteomics program, established in 2004, aims to characterize the pathogen and host cell proteome by identifying proteins associated with the biology of microbes, mechanisms of microbial pathogenesis and host responses to infection, thereby facilitating the discovery of target genes or proteins as potential candidates for the generation of vaccines, therapeutics, and diagnostics [1]
The Proteomics Research Centers (PRCs) work on many different organisms, covering bacterial pathogens (Bacillus anthracis, Brucella abortus, Francisella tularensis, Salmonella typhi, S. typhimurium, Vibrio cholerae, Yersinia pestis), Eukaryotic parasites (Cryptosporidium parvum, Toxoplasma gondii), and viral pathogens (Monkeypox, SARS-CoV, Vaccinia)
The centers have generated a heterogeneous set of experimental data using various technologies loosely defined as proteomic, but encompassing genomic, structural, immunology and protein interaction technologies, as well as more standard cell and molecular biology techniques used to validate potential targets identified via high-throughput methods
Summary
Reemerging infectious diseases, as well as a Biodefense Resource Center for public dissemination of the pathogen and host data, biological reagents, protocols, and other project deliverables. The centers have generated a heterogeneous set of experimental data using various technologies loosely defined as proteomic, but encompassing genomic, structural, immunology and protein interaction technologies, as well as more standard cell and molecular biology techniques used to validate potential targets identified via high-throughput methods. The PRCs have provided biological reagents such as clones, antibodies and engineered bacterial strains, other deliverables include standard operating procedures (SOPs) and new technologies such as instrumental methods and software tools and publications related to all of these activities. Due to the breadth of the program, the potential user community is quite broad, from technology or informatics experts who may want to reanalyze the data or develop better algorithms, to a wide group of biomedical scientists who are interested in mining the data for their own studies or just finding new information on a protein or gene of interest quickly and
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