Pan-Genomic Approaches for Comprehensive Screening of Novel or Emerging Infectious Agents in Blood Emerging infectious agents, the latest of which is Zika virus, continually threaten the safety of the 15 million transfusions performed annually in the United States, yet the lack of diagnostic tools to comprehensively test for all bloodborne pathogens or to identify infections from novel viruses has greatly hindered surveillance efforts. In a previous grant, we have pioneered the development of microarray and metagenomic sequencing-based approaches to comprehensively screen blood for both known and novel pathogens, and have identified a number of novel viruses circulating in human blood. We have established long-term collaborations with national and international collaborators who will provide us with clinical and donor blood samples from individuals infected with chikungunya, dengue, Ebola, Zika, Lassa, and West Nile virus, as well as non-viral pathogens (e.g. Babesia microti and Plasmodium falciparum), for analysis. This project proposes (1) to develop an accurate and comprehensive yet practical sequencing-based platform (BloodSeq) for simultaneous detection and whole-genome characterization of all American Association of Blood Banks (AABB)-priority pathogens in infected patients and blood donations, (2) to discover and further describe the epidemiology and potential pathogenicity of novel infectious viruses that pose a potential threat of bloodborne transmission, and (3) to define complementary host response biosignatures for transfusion-transmissible pathogens using transcriptome profiling, especially in asymptomatic infected donors. A key deliverable from this 5-year project will be implementation of the BloodSeq platform by public health agencies such as the American Red Cross for comprehensive bloodborne pathogen screening of the blood supply.The results from these studies will advance genomic sequencing technologies as validated screening tools to ensure transfusion safety, with significant clinical and public health implications.

Public Health Relevance

Pan-Genomic Approaches for Comprehensive Screening of Novel or Emerging Infectious Agents in Blood Outbreaks from emerging infectious agents, including Zika and Ebola virus, continually threaten the safety of the 15 million transfusions performed annually in the United States, but we lack diagnostic tools to comprehensively screen for these bloodborne pathogens. Here, we propose develop, validate, and implement pan-genomic approaches to screen for known or novel infectious agents in transfused blood. These include a BloodSeq sequencing platform that enables simultaneous detection of all American Association of Blood Banks (AABB)-priority pathogens, characterization of novel infectious viruses circulating in blood, and identification of human host response biosignatures for bloodborne infections in both symptomatic and asymptomatic individuals.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-VH-D (55)R)
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Zou, Shimian
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Bouquet, Jerome; Soloski, Mark J; Swei, Andrea et al. (2016) Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease. MBio 7:e00100-16
Greninger, Alexander L; Chatterjee, Som S; Chan, Liana C et al. (2016) Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance. PLoS One 11:e0149541
Naccache, Samia N; Thézé, Julien; Sardi, Silvia I et al. (2016) Distinct Zika Virus Lineage in Salvador, Bahia, Brazil. Emerg Infect Dis 22:1788-92
Greninger, Alexander L; Naccache, Samia N; Messacar, Kevin et al. (2015) A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis 15:671-82
Greninger, Alexander L; Messacar, Kevin; Dunnebacke, Thelma et al. (2015) Clinical metagenomic identification of Balamuthia mandrillaris encephalitis and assembly of the draft genome: the continuing case for reference genome sequencing. Genome Med 7:113
Greninger, Alexander L; Naccache, Samia N; Federman, Scot et al. (2015) Rapid metagenomic identification of viral pathogens in clinical samples by real-time nanopore sequencing analysis. Genome Med 7:99
Luk, Ka-Cheung; Berg, Michael G; Naccache, Samia N et al. (2015) Utility of Metagenomic Next-Generation Sequencing for Characterization of HIV and Human Pegivirus Diversity. PLoS One 10:e0141723
Chiu, Charles Y; Bres, Vanessa; Yu, Guixia et al. (2015) Genomic Assays for Identification of Chikungunya Virus in Blood Donors, Puerto Rico, 2014. Emerg Infect Dis 21:1409-13
Saglam, Ozlen; Samayoa, Erik; Somasekar, Sneha et al. (2015) No viral association found in a set of differentiated vulvar intraepithelial neoplasia cases by human papillomavirus and pan-viral microarray testing. PLoS One 10:e0125292
Deng, Xutao; Naccache, Samia N; Ng, Terry et al. (2015) An ensemble strategy that significantly improves de novo assembly of microbial genomes from metagenomic next-generation sequencing data. Nucleic Acids Res 43:e46

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