Project description:<p>The overall purpose of this study is to investigate the host genetic factors in response to influenza virus infection, with the focus on influenza vaccination in the first substudy "Adult Influenza Vaccine Genetics" and with the focus on influenza natural infection and other acute respiratory infections (ARIs) in the second substudy "Acute Viral Respiratory Infection Genetics". In the first substudy, healthy adults were enrolled in 2008 (male cohort) and 2010 (female cohort) and immunized with seasonal influenza vaccine. In the second substudy, healthy adults were invited to enroll to be followed for acute respiratory illness through two consecutive influenza seasons 2009-2010 and 2010-2011. Peripheral blood genomic DNA samples were collected from all the subjects, and time-series RNA and serum samples were obtained pre- and post- immunization/infection. Genotyping was carried out on peripheral blood genomic DNA samples using Illumina HumanOmniExpress-12 v1 arrays. Peripheral blood RNA samples obtained at each visit were analyzed using Illumina Human HT-12 (for all the samples) and HiSeq 2000 (for 130 samples in the "Acute Viral Respiratory Infection Genetics" study). Serum specimens were tested using hemagglutination-inhibition (HAI) antibody assay for Influenza H1N1, H3N2, and Influenza B strains.</p> <p>A detailed description of each substudy is provided under their own pages below and via the grouping tool in the right-hand box: <ul> <li><a href="./study.cgi?study_id=phs000635">phs000635</a> Adult Influenza Vaccine Genetics</li> <li><a href="./study.cgi?study_id=phs001031">phs001031</a> Acute Viral Respiratory Infection Genetics</li> </ul> </p>
Project description:A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach. Patients with respiratory tract infection along with ill, non-infected controls were enrolled through the emergency department or undergraduate student health services. Whole blood was obtained to generate gene expression profiles. These profiles were then used to generate signatures of bacterial acute respiratory infection, viral acute respiratory infection, and non-infectious illness. 273 subjects were ascertained for this analysis. This included 88 patients with non-infectious illness, 115 with viral acute respiratory infection, and 70 with bacterial acute respiratory infection. Samples were obtained at the time of enrollment, which was at initial clinical presentation. Total RNA was extracted from human blood using the PAXgene Blood RNA Kit. Microarray data were generated using the GeneChip Human Genome U133A 2.0 Array. Microarrays were generated in two microarray batches with seven overlapping samples giving rise to 280 total microarray experiments.
Project description:A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach. Patients with respiratory tract infection along with ill, non-infected controls were enrolled through the emergency department or undergraduate student health services. Whole blood was obtained to generate gene expression profiles. These profiles were then used to generate signatures of bacterial acute respiratory infection, viral acute respiratory infection, and non-infectious illness.
Project description:Diagnosis of acute respiratory viral infection is currently based on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with viral respiratory infection represents a novel means of infection diagnosis. We used microarrays to capture peripheral blood gene expression at baseline and time of peak symptoms in healthy volunteers infected intranasally with influenza A H3N2, respiratory syncytial virus or rhinovirus. We determined groups of coexpressed genes that accurately classified symptomatic versus asymptomatic individuals. We experimentally inoculated healthy volunteers with intranasal influenza, respiratory syncytial virus or rhinovirus. Symptoms were documented and peripheral blood samples drawn into PAXgene tubes for RNA isolation.
Project description:Diagnosis of acute respiratory viral infection is currentlybased on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with viral respiratory infection represents a novel means of infection diagnosis. We used microarrays to capture peripheral blood gene expression at baseline and time of peak symptoms in healthy volunteers infected intranasally with influenza A H3N2, respiratory syncytial virus or rhinovirus. We determined groups of coexpressed genes that accurately classified symptomatic versus asymptomatic individuals.