Metabolic biomarkers and biosignatures for improved diagnosis of Lyme disease

用于改善莱姆病诊断的代谢生物标志物和生物特征

• 批准号: 8841454
• 负责人: John T Belisle
• 金额: $ 45.55万
• 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: 2014-06-10 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8841454
• 关键词: Amoxicillin; Antibiotics; Antigens; Bacteria; Biochemistry; Bioinformatics; Biological Assay; Biological Markers; Bite; Borrelia burgdorferi; Cancer Biology; Centers for Disease Control and Prevention (U.S.); Characteristics; Chemical Structure; Chronic; Clinical; Collaborations; Colorado; Communicable Diseases; Complex; Computer software; DNA; Data; Data Set; Deposition; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Doxycycline; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Etiology; Europe; Evaluation; Exanthema; FDA approved; Goals; Growth; Human; Individual; Infection; Laboratories; Lead; Logistic Regressions; Lyme Disease; Malignant Neoplasms; Mass Spectrum Analysis; Metabolic; Metabolic Diseases; Methods; Modeling; Molecular; Monitor; Morbidity - disease rate; New York; Order Spirochaetales; Patients; Phase; Phased Innovation Awards; Process; Qualifying; Reporting; Research; Resources; Sampling; Scientist; Serologic tests; Serum; Site; Source; Specificity; Staging; Standardization; Technical Expertise; Techniques; Technology; Testing; Ticks; United States; Universities; Urine; Vector-transmitted infectious disease; Visual; Western Blotting; base; biological systems; biosignature; comparative; disorder prevention; erythema migrans; improved; innovation; instrumentation; latent infection; medical schools; metabolomics; novel; novel diagnostics; pathogen; skin lesion; small molecule; tool; tool development; tuberculosis treatment

Summary Lyme disease (LD) is the most commonly reported vector-borne disease in the United States with approximately 38,000 confirmed and probable cases in 2009. The currently recommended method for diagnosing LD is a two-tiered serology-based test that is limited in its ability to differentiate active from previous infection, diagnose early LD, and is not standardized among laboratories. These limitations can result in misinterpretations and have led to millions of diagnostic tests (FDA approved and non-approved) being performed each year for this infection. Thus, a fresh approach for improved diagnostic development is critical to the field. Studies applying the global evaluation of small molecule biomarkers, "metabolomics", for the discovery of biosignatures and biomarkers for monitoring cancers and metabolic diseases have shown tremendous promise. Although this technology has not been widely applied for infectious diseases, it is recognized that infectious diseases are manifested based on alterations to the biochemistry of a biological system. Thus, as is now being shown with other infections, we hypothesize that metabolomics offers an innovative approach for identification of biosignatures and biomarkers of LD. This R21/R33 application proposes to, in the first two years, elucidate multiple metabolome-based biosignatures of LD; initiate identification of products that comprise these biosignatures; and establish tools for the elucidation of the Borrelia burgdorferi metabolome. Successful completion of these initial studies and tool development efforts will lead to efforts in Years 3-5 to qualify the LD biosignatures; complete the molecular identification of the biosignature products; and provide a comprehensive analysis of the B. burgdorferi metabolome. These activities encompassing the entirety of the R21/R33 program are framed within three Specific Aims: 1) Develop and qualify metabolic biosignatures that differentiate active LD from look-alike infections, and define the stages of disease including cured LD; 2) Identify and validate the chemical structures of the metabolites that comprise the biosignatures of LD; and 3) Evaluate the metabolic profile of B. burgdorferi. The overall goal at the end of five years will be to have qualified LD biosignatures that can be applied in clinical laboratories using mass spectrometry or another analytical technique suitable for a multi-analyte small molecule diagnostic.

概括 莱姆病（LD）是美国最常见的载体传播疾病 2009年约有38,000个确认案例。 诊断LD是一项两层基于血清学的测试，其与以前的活动能力有限 感染，诊断早​​期LD，在实验室中不标准化。这些限制可能导致 误解，导致数百万诊断测试（FDA批准和未批准） 每年为此感染进行。因此，改进诊断开发的新方法至关重要 到田野。应用小分子生物标志物“代谢组学”的全球评估的研究 发现用于监测癌症和代谢疾病的生物签名和生物标志物已显示 巨大的希望。尽管该技术尚未广泛应用于传染病，但这是 认识到传染病是基于生物化学的改变而表现出来的 系统。因此，正如现在与其他感染所显示的那样，我们假设代谢组学提供了 鉴定LD生物签名和生物标志物的创新方法。此R21/R33应用程序 在最初的两年中，建议阐明LD的多个基于代谢组的生物签名。发起 鉴定构成这些生物签名的产品；并建立阐明的工具 Borrelia Burgdorferi代谢组。这些初步研究和工具开发工作成功完成 将导致3 - 5年的努力使LD生物签名合格；完成分子鉴定 生物签名产品；并提供对B. burgdorferi代谢组的全面分析。这些 涵盖R21/R33计划的整个活动的活动是在三个特定目标中构建的：1） 并有资格将活性LD与外观感染区分开并定义阶段的代谢生物签名 包括治愈LD在内的疾病； 2）识别和验证构成代谢物的化学结构 LD的生物签名； 3）评估B. burgdorferi的代谢谱。结束的总体目标 五年将拥有合格的LD生物签名，可以使用质量应用于临床实验室 光谱法或另一种适用于多分析物小分子诊断的分析技术。