Digital serology for parallel parasitic disease detection

用于并行寄生虫病检测的数字血清学

基本信息

批准号：
9255416
负责人：
Patrick S Daugherty
金额：
$ 22.5万
依托单位：
SERIMMUNE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9255416
关键词：
Acanthamoeba Acute Disease Address Americas Angiostrongylus cantonensis Antibodies Antibody Repertoire Antibody Specificity Antigen Targeting Antigens Archives Autoimmune Diseases Balamuthia mandrillaris Bar Codes Binding Bioinformatics Biological Assay Blinded Blood Cells Blood Tests Cardiac Celiac Disease Centers for Disease Control and Prevention (U.S.)Chagas Disease Chronic Chronic Disease Clinical Collection Communicable Diseases Computer software Consensus Custom Data Data Set Databases Detection Diagnosis Diagnostic Diagnostic Sensitivity Diagnostic Specificity Diagnostic tests Disease Echinococcus granulosus Entamoeba histolytica Enzyme-Linked Immunosorbent Assay Epitopes Exhibits Family Gold Heart Diseases Human Immunoassay Individual Infection Knowledge Laboratories Lead Leishmania Measures Methodology Methods Microscopic Naegleria fowleri Outcome Parasites Parasitic Diseases Parasitic infection Peptide Library Peptides Phase Populations at Risk Preparation Process Randomized Reproducibility Sampling Sensitivity and Specificity Serodiagnoses Serologic tests Serological Specificity Specimen Taenia solium Technology Test Result Testing Time Toxocara Toxoplasma gondii Trypanosoma cruzi United States Validation accurate diagnosis base biomarker discovery cost diagnostic accuracy diagnostic panel digital gastrointestinal improved molecular diagnostics neglect next generation sequencing novel pathogen performance tests prevent specific biomarkers

项目摘要

The proposed project aims to build a diagnostic test for chronic T. cruzi infection and Chagas disease that not only improves testing performance but that can be readily integrated with similarly developed tests for most clinically important parasitoses. Current assays for Chagas disease, and other parasitic infections, lack desired levels of specificity, and require multiple independent assays and testing formats. Consequently, testing a single specimen for several different clinically important parasitic diseases becomes cost prohibitive and time consuming, delaying disease detection and treatment. We propose to address this problem by creating a single, all-in-one diagnostic test able to detect ten or more different clinically important parasitic diseases. Importantly, the proposed strategy could be expanded to a nearly arbitrary number of infectious diseases without resultant increases in final test cost. Towards a multiplexed parasitic disease test, we will first create an improved test for Chagas disease, that impacts about 350,000 individuals in the US, and 8 million in the Americas. To accomplish this, we will apply bacterial display peptide libraries, next-generation sequencing, and computational bioinformatics to identify a set of motifs and consensus peptides corresponding to antigenic peptide epitopes that when combined yield optimal sensitivity and specificity values in the discovery set. The motif and peptide panels will be validated using an independent specimen set. Assay reproducibility and stability will be measured. This project may thus lead to clinically useful tests to improve the rates of detection parasitic diseases their resultant complications.

拟议项目旨在建立一种针对慢性克氏锥虫感染和恰加斯病的诊断测试，不仅提高测试性能，而且可以轻松地与大多数临床重要寄生虫的类似开发测试集成。目前针对恰加斯病和其他寄生虫感染的检测缺乏所需的特异性水平，并且需要多种独立的检测和测试形式。因此，对单个样本进行几种不同的临床上重要的寄生虫病的检测变得成本高昂且耗时，从而延误了疾病的检测和治疗。我们建议通过创建一种单一的、一体化的诊断测试来解决这个问题，该测试能够检测十种或更多不同的临床上重要的寄生虫病。重要的是，所提出的策略可以扩展到几乎任意数量的传染病，而不会导致最终测试成本增加。为了进行多重寄生虫病测试，我们将首先创建一种改进的恰加斯病测试，该病影响美国约 35 万人，美洲约 800 万人。为了实现这一目标，我们将应用细菌展示肽文库、下一代测序和计算生物信息学来识别与抗原肽表位相对应的一组基序和共有肽，这些基序和共有肽组合起来在发现组中产生最佳的灵敏度和特异性值。基序和肽组将使用独立的样本集进行验证。将测量测定的重现性和稳定性。因此，该项目可能会带来临床上有用的测试，以提高寄生虫病及其并发症的检出率。