双重、系统的疟疾诊断生物标志物发现方法。
A Dual, Systematic Approach to Malaria Diagnostic Biomarker Discovery.
机构信息
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana.
出版信息
Clin Infect Dis. 2022 Jan 7;74(1):40-51. doi: 10.1093/cid/ciab251.
BACKGROUND
The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests (RDTs) prompted the World Health Organization and other global health stakeholders to prioritize the discovery of novel diagnostic biomarkers for malaria.
METHODS
To address this pressing need, we adopted a dual, systematic approach by conducting a systematic review of the literature for publications on diagnostic biomarkers for uncomplicated malaria and a systematic in silico analysis of P. falciparum proteomics data for Plasmodium proteins with favorable diagnostic features.
RESULTS
Our complementary analyses led us to 2 novel malaria diagnostic biomarkers compatible for use in an RDT format: glyceraldehyde 3-phosphate dehydrogenase and dihydrofolate reductase-thymidylate synthase.
CONCLUSIONS
Overall, our results pave the way for the development of next-generation malaria RDTs based on new antigens by identifying 2 lead candidates with favorable diagnostic features and partially de-risked product development prospects.
背景
缺乏 HRP2/3 蛋白的恶性疟原虫寄生虫的出现和传播，以及由此导致 HRP2 为基础的疟疾快速诊断检测（RDT）的实用性降低，促使世界卫生组织和其他全球卫生利益相关者优先发现疟疾的新型诊断生物标志物。
方法
为了满足这一紧迫需求，我们采用了双重、系统的方法，对文献中关于无并发症疟疾诊断生物标志物的出版物进行了系统综述，并对恶性疟原虫蛋白质组学数据进行了系统的计算机分析，以寻找具有良好诊断特征的疟原蛋白。
结果
我们的互补分析使我们找到了 2 种适合 RDT 格式的新型疟疾诊断生物标志物：甘油醛 3-磷酸脱氢酶和二氢叶酸还原酶-胸苷酸合酶。
结论
总的来说，我们的结果通过确定 2 种具有良好诊断特征和部分降低产品开发风险的候选物，为基于新抗原的下一代疟疾 RDT 的开发铺平了道路。
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