Metabolomics-based discovery of small molecule biomarkers for noninvasive dengue

基于代谢组学的非侵入性登革热小分子生物标志物的发现

• 批准号: 8841436
• 负责人: Rushika Perera
• 金额: $ 40.29万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8841436
• 关键词: Acute; Affect; Algorithms; Bedside Testings; Biological; Biological Markers; Blood specimen; California; Cell physiology; Cells; Cessation of life; Childhood; Clinical; Clinical Course of Disease; Clinical Data; Clinical Research; Clinics and Hospitals; Cohort Studies; Colorado; Communities; Computer software; Country; Databases; Dengue; Dengue Hemorrhagic Fever; Dengue Virus; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Outcome; Environment; Epidemic; Fingerprint; Funding Mechanisms; Generations; Goals; Health; Hemorrhagic Shock; Hospitals; Immunoglobulin M; Individual; Industry; Infection; Laboratories; Latin America; Liquid Chromatography; Liquid substance; Machine Learning; Mass Spectrum Analysis; Metabolic; Metabolic Pathway; Metabolism; Mexico; Molecular; Molecular Weight; Multivariate Analysis; Nicaragua; Nicaraguan; Patient Care; Patient Care Management; Patient Triage; Patients; Phase; Physicians; Physiological; Prognostic Marker; Public Health; Qualifying; Regimen; Reporting; Research; Risk; Saliva; Sampling; Scientist; Sensitivity and Specificity; Serum; Shock; Signs and Symptoms; Specimen; Supportive care; Syndrome; System; Testing; Therapeutic Intervention; Tissues; Universities; Urine; Virus Diseases; base; clinical care; disease diagnosis; innovation; liquid chromatography mass spectrometry; metabolomics; outcome forecast; point-of-care diagnostics; prognostic; programs; prospective; small molecule; tandem mass spectrometry

PROJECT SUMMARY / ABSTRACT Epidemic dengue fever (DF) and dengue hemorrhagic fever (DHF/DSS) have emerged throughout the tropical world with devastating public health consequences. A dramatic increase in severe dengue disease (DEN) in Latin America in the last decade is of grave concern; 30% of cases are now diagnosed as severe dengue virus (DENV) infections. DEN is overwhelming public health capacity for clinical care in much of the developing world. The overall goal of this proposal is to provide a major change in the diagnosis and prognosis (D&P) of DENV infections. A metabolomics approach will be used to identify candidate metabolite small molecule biomarkers (SMBs) that occur both in serum and in non-invasive clinical specimens (urine and saliva) that diagnose DENV infection and predict progression to severe disease. Preliminary studies using acute phase specimens from DEN patients have identified a number of molecular features and candidate SMBs of DF and DHF/SS in serum, saliva, and urine using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. In the R21 phase of this project, we will use a metabolic fingerprinting approach to confim existing and identify new candidate SMBs in retrospectively collected serum specimens available from the high-quality pediatric DEN hospital-based and cohort studies in Nicaragua, will begin to characterize the SMBs and metabolic pathways involved, will investigate the efficacy for D&P of these SMBs in prospectively collected serum, saliva, and urine specimens in the hospital study, and will identify a portfolio of the most significant molecular features that differentiate DEN, severe DEN, and non-DEN disease. We will develop algorithms including SMBs, clinical signs and symptoms, and clinical laboratory results for the D&P of DENV infections. In the R33 phase of the project, prospectively collected serum, saliva, and urine samples from both the hospital study and a community-based cohort study will be analyzed by metabolic profiling using LC-tandem MS (LC- MS/MS) to identify candidate SMBs. First generation EIA tests for selected SMBs will be included in the diagnostic regimen in Nicaragua The diagnostic and prognostic sensitivity and specificity of the candidate SMBs and "first generation" SMB tests will be determined as will the preferred clinical specimen for SMB- based diagnoses. Overall these studies will identify a panel of SMBs (e.g., 5-10), which will be used to formulate the Target Product Profiles (TPP) for rapid point-of-care (POC) tests for use in clinics and hospitals for DEN D&P. Detection of SMBs in saliva and urine that are predictive of severe DEN is innovative and provides the opportunity for a true paradigm shift in diagnosis by using inexpensive, easily procured, non- invasive clinical specimens for D&P of DEN.

项目摘要/摘要