Mahadevan P.,George Mason University |
Seto J.,George Mason University |
Tibbetts C.,Tessarae, Llc |
Seto D.,George Mason University
Virology | Year: 2010
Human adenovirus type 3 (HAdV-B3) has an apparently stable genome yet remains a major circulating and problematic respiratory pathogen. Comparisons of the prototype genome to genomes from three current field strains, including two isolated from epidemics, and a laboratory strain, yielded small-scale nucleotide variations across 50 years of time and space (U.S. and China). This is in contrast to the recombination events that have been reported recently for HAdV genomes. Recombinant genomes have been identified in emergent HAdV pathogens and is a pathway for the molecular evolution of types. These two contrasting views of HAdV genome stability have repercussions in the development and use of vaccines for countering HAdV-B3, as well as in the continued effectiveness of vaccines developed against earlier and current circulating types of HAdV. © 2009 Elsevier Inc. All rights reserved.
Wang Z.,Center for Bio Molecular Science and Engineering |
Malanoski A.P.,Center for Bio Molecular Science and Engineering |
Lin B.,Center for Bio Molecular Science and Engineering |
Long N.C.,Nova Research Inc. |
And 10 more authors.
Microbial Ecology | Year: 2010
Military recruits experience a high incidence of febrile respiratory illness (FRI), leading to significant morbidity and lost training time. Adenoviruses, group A Streptococcus pyogenes, and influenza virus are implicated in over half of the FRI cases reported at recruit training center clinics, while the etiology of the remaining cases is unclear. In this study, we explore the carriage rates and disease associations of adenovirus, enterovirus, rhinovirus, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis in military recruits using high-density resequencing microarrays. The results showed that rhinoviruses, adenoviruses, S. pneumoniae, H. influenzae, and N. meningitidis were widely distributed in recruits. Of these five agents, only adenovirus showed significant correlation with illness. Among the samples tested, only pathogens associated with FRI, such as adenovirus 4 and enterovirus 68, revealed strong temporal and spatial clustering of specific strains, indicating that they are transmitted primarily within sites. The results showed a strong negative association between adenoviral FRI and the presence of rhinoviruses in recruits, suggesting some form of viral interference. © 2010 Springer Science+Business Media, LLC.
Kourout M.,OBRR |
Fisher C.,OBRR |
Purkayastha A.,Tessarae, Llc |
Tibbetts C.,Tessarae, Llc |
And 4 more authors.
Transfusion | Year: 2016
BACKGROUND The implementation of nucleic acid-based tests for blood donor screening has improved the safety of the blood supply; however, the increasing number of emerging pathogen tests is burdensome. Development of multiplex testing platforms that allow simultaneous screening for different pathogens is a potential solution. STUDY DESIGN AND METHODS The TessArray resequencing microarray is a platform that allows multiplex detection and identification of 97 different blood-borne pathogens in one single test. The objective was to evaluate the lowest concentration detected in blood or plasma, species discrimination, and applicability of the TessArray microarray platform for testing blood donors. Human blood or plasma spiked with selected pathogens (10,000, 1000, or 100 cells or copies/mL), including three viral, four bacterial, and four protozoan pathogens were each tested on this platform. The nucleic acids were extracted, amplified using multiplexed sets of pooled specific primers, fragmented, labeled, and hybridized to a microarray. Finally, the detected sequences were identified using an automated genomic database alignment algorithm. RESULTS The performance of this platform demonstrated detection for spiked bacterial and protozoan pathogens of 100 cells/mL and viral pathogens as low as 100 copies/mL. Coded specimens, including spiked and negative controls, were identified correctly for blood specimens (31/32, 97%) and for plasma specimens (20/22, 91%) demonstrating the effectiveness of the platform. CONCLUSION These results indicated that the TessArray microarray platform could be employed for multiplex detection and identification, with a high level of discriminatory power for numerous blood-borne pathogen targets with potential for use in blood safety. © 2016 AABB.
Abd Rahman S.,University of Queensland |
Schirra H.J.,University of Queensland |
Lichanska A.M.,University of Queensland |
Lichanska A.M.,Tessarae, Llc |
And 3 more authors.
Growth Hormone and IGF Research | Year: 2013
Objective: Growth hormone (GH) is a protein hormone with important roles in growth and metabolism. The objective of this study was to investigate the metabolism of a human subject with severe GH deficiency (GHD) due to a PIT-1 gene mutation and the metabolic effects of GH therapy using Nuclear Magnetic Resonance (NMR)-based metabonomics. NMR-based metabonomics is a platform that allows the metabolic profile of biological fluids such as urine to be recorded, and any alterations in the profile modulated by GH can potentially be detected. Design: Urine samples were collected from a female subject with severe GHD before, during and after GH therapy, and from healthy age- and sex-matched controls and analysed with NMR-based metabonomics. Setting: The samples were collected at a hospital and the study was performed at a research facility. Participants: We studied a 17. year old female adolescent with severe GHD secondary to PIT-1 gene mutation who had reached final adult height and who had ceased GH therapy for over 3. years. The subject was subsequently followed for 5. years with and without GH therapy. Twelve healthy age-matched female subjects acted as control subjects. Intervention: The GH-deficient subject re-commenced GH therapy at a dose of 1. mg/day to normalise serum IGF-1 levels. Main outcome measures: Urine metabolic profiles were recorded using NMR spectroscopy and analysed with multivariate statistics to distinguish the profiles at different time points and identify significant metabolites affected by GH therapy. Results: NMR-based metabonomics revealed that the metabolic profile of the GH-deficient subject altered with GH therapy and that her profile was different from healthy controls before, and during withdrawal of GH therapy. Conclusion: This study illustrates the potential use of NMR-based metabonomics for monitoring the effects of GH therapy on metabolism by profiling the urine of GH-deficient subjects. Further controlled studies in larger numbers of GH-deficient subjects are required to determine the clinical benefits of NMR-based metabonomics in subjects receiving GH therapy. © 2012 Elsevier Ltd.
Tessarae, Llc and The Regents Of The University Of California | Date: 2013-02-21
A robust, automated computational pipeline was used to design a system comprising a microarray for the identification of microorganisms and their antibiotic resistance profiles. This system and methods will facilitate the study of the epidemiology and microbial ecology of antibiotic resistance and be an invaluable tool to rapidly and simultaneously identify organisms and their antimicrobial resistance elements in environmental, food and clinical samples.
Tanner A.K.,Emory University |
Valencia C.A.,Emory University |
Rhodenizer D.,Emory University |
Espirages M.,Emory University |
And 12 more authors.
Journal of Molecular Diagnostics | Year: 2014
Identifying individuals as carriers of severe disease traits enables informed decision making about reproductive options. Although carrier screening has traditionally been based on ethnicity, the increasing ethnic admixture in the general population argues for the need for pan-ethnic carrier screening assays. Highly multiplexed mutation panels allow for rapid and efficient testing of hundreds of mutations concurrently. We report the development of the Pan-Ethnic Carrier Screening assay, a targeted sequencing assay for routine screening that simultaneously detects 461 common mutations in 91 different genes underlying severe, early-onset monogenic disorders. Mutation selection was aided by the use of an extensive mutation database from a clinical laboratory with expertise in newborn screening and lysosomal storage disease testing. The assay is based on the Affymetrix GeneChip microarray platform but generates genomic DNA sequence as the output. Analytical sensitivity and specificity, using genomic DNA from archived control cultures and from clinical specimens, was found to be >99% for all mutation types. This targeted sequencing assay has advantages over multiplex PCR and next-generation sequencing assays, including accuracy of mutation detection over a range of mutation types and ease of analysis and reporting of results. © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology.
PubMed | Tessarae, Llc and Emory University
Type: Journal Article | Journal: The Journal of molecular diagnostics : JMD | Year: 2014
Identifying individuals as carriers of severe disease traits enables informed decision making about reproductive options. Although carrier screening has traditionally been based on ethnicity, the increasing ethnic admixture in the general population argues for the need for pan-ethnic carrier screening assays. Highly multiplexed mutation panels allow for rapid and efficient testing of hundreds of mutations concurrently. We report the development of the Pan-Ethnic Carrier Screening assay, a targeted sequencing assay for routine screening that simultaneously detects 461 common mutations in 91 different genes underlying severe, early-onset monogenic disorders. Mutation selection was aided by the use of an extensive mutation database from a clinical laboratory with expertise in newborn screening and lysosomal storage disease testing. The assay is based on the Affymetrix GeneChip microarray platform but generates genomic DNA sequence as the output. Analytical sensitivity and specificity, using genomic DNA from archived control cultures and from clinical specimens, was found to be >99% for all mutation types. This targeted sequencing assay has advantages over multiplex PCR and next-generation sequencing assays, including accuracy of mutation detection over a range of mutation types and ease of analysis and reporting of results.
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 89.65K | Year: 2010
National swine health statistics indicate a growing death rate due to respiratory disease in both the nursery and grower/finished phases in swine (Swine 2006, APHIS, USDA). In 2006, veterinary diagnostic testing revealed that Porcine Reproductive and Respiratory Syndrome was the most prevalent of the diagnosed diseases in breeding herd and nursery pigs (Swine 2006, APHIS, USDA). Additional diseases that contribute to the swine morbidity and mortality rate include Porcine Circovirus 2 associated diseases, swine influenza, foot and mouth disease, classic swine fever and swine vesicular disease. The proposed TessArray RPM assay is a simultaneously differential diagnosis platform for these and other targeted pathogens of the assay. The single test result can establish cause of infectious disease in individual animals as well as outbreaks of infectious disease in local herds or across swine production communities. No existing test other than RPM can enable rapid differential diagnosis, determine presence of multiple infectious agents co-infecting individual animals, or support epidemiological tracking in epidemic outbreaks to minimize effective response times.
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 460.00K | Year: 2011
The primary objectives of this Phase II project are to 1) validate performance of the prototype resequencing pathogen microarray application for detection and identification of selected food-borne pathogens, including varieties of viruses, bacteria and eukaryotic agents; 2) iterate and port the prototype application to a more practical, "market-friendly" product form factor that requires less expensive capital equipment to use, and that anticipates significantly lower operating cost per assay, without compromise of assay multiplicity, sensitivity or specificity; and 3) perform limited additional performance validation of the product application to enable initial commercial marketing to government and private sector, domestic and international laboratories that provide food-safety testing services.
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 79.68K | Year: 2009
Most contemporary diagnostic tests are designed to detect and identify a single particular pathogen if it may be present in a given specimen. Furthermore such assays typically rely upon a short biomarker, or short signature gene sequence element to INDIRECTLY determine if the specimen is or is not present in the specimen. Such assays are inevitably vulnerable to false negative or false positive reports that can have costly implications from poorly informed decisions in critical food safety situations. In distinct contrast the DIRECT determination of multiple gene sequences from one or more target pathogens can provide unequivocal evidence for the presence or absence of multiple pathogens that may be associated with a particular food safety-related specimen. Furthermore such gene sequences, as opposed to a measured signal intensity from a traditional biomarker assay, provide direct information on the specific strains and variants of pathogens that may be detected, and identification in such detail to support forensic epidemiology or tracking of a chain of breakdowns food-safety. The re-sequencing microarray is a DIRECT DNA sequencing technology that is most efficient at providing accurate gene sequences for hundreds of target pathogen genes in each assay. This Phase I project will develop a prototype resequencing microarray-based diagnostic assay for general application in food-safety. If superior assay performance is demonstrated and validated as may be expected, then this prototype assay has excellent potential for commercialization in broad food-safety related applications. The product will demonstrate significantly superior performance compared to traditional microbial culture or more recent molecular diagnostic assays (e.g. PCR).