Jaqueline Volpe,Floriatan S Costa,Beatriz Sachuk,Isabela Camilo,Angélica Faria,Hélida M de Andrade,Saimon M Silva,Dênio Souto
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This study presents an SPR biosensor with SOM analysis to enhance serodiagnosis of canine visceral leishmaniasis (CVL), a neglected tropical disease, whose delayed and inadequate detection in human and canine populations compromises effective disease control. The reaction kinetics of PQ20, a multiepitope chimeric protein with 20 B- and T-cell epitopes, with anti-PQ20 was evaluated. The proposed mechanism suggests two immunodominant epitopes of PQ20 through its reaction with polyclonal antibodies of Leishmania chagasi, presenting high initial association rates (ka1 = 2.4 × 105 L mol-1 s-1; kd1 = 5.5 × 10-4 L mol-1 s-1). The biosensor's diagnostic performance was evaluated, achieving a 5.1 nmol L-1 detection limit. SOM clustering indicated a higher specificity at shorter reaction times, supporting reduced diagnostic timelines (100 s) in accordance with kinetic evaluation. Finally, SOM-based data interpretation improved sensitivity and specificity compared to univariate analysis in raw serum, enhancing the assay's ability to classify samples in more complex media, in less than 15 min analysis time. 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引用次数: 0
摘要
在资源有限的环境中,生物传感器是一种很有前途的、具有成本效益的传染病诊断方法,既不需要实验室基础设施,也不需要专业人员。基于表面等离子体共振(SPR)的生物传感器在无标记、实时分析生物相互作用和动力学参数确定方面仍然是卓越的。集成人工智能(AI),特别是自组织地图(SOMs),通过将高维数据投射到保持拓扑的二维地图上,自动进行感染筛查,通过实现感染与健康患者的有效分类,为诊断策略提供优势。本研究提出了一种带有SOM分析的SPR生物传感器,用于提高犬内脏利什曼病(CVL)的血清诊断,CVL是一种被忽视的热带病,其在人类和犬群体中的延迟和不充分的检测影响了有效的疾病控制。研究了具有20个B细胞和t细胞表位的多表位嵌合蛋白PQ20与抗PQ20的反应动力学。PQ20通过与查加斯利什曼原虫多克隆抗体反应产生两个免疫优势表位,具有较高的初始关联率(ka1 = 2.4 × 105 L mol-1 s-1; kd1 = 5.5 × 10-4 L mol-1 s-1)。对生物传感器的诊断性能进行了评价,检测限为5.1 nmol L-1。SOM聚类在更短的反应时间内显示出更高的特异性,支持根据动力学评估缩短诊断时间(100秒)。最后,与原始血清中的单变量分析相比,基于som的数据解释提高了敏感性和特异性,增强了该分析在不到15分钟的分析时间内对更复杂介质中的样品进行分类的能力。将多表位生物受体与人工智能驱动的分析相结合,可提供快速且无标记的CVL监测,在这种传染病的管理中具有更广泛的应用。
Interpretating SPR-Derived Reaction Kinetics via Self-Organizing Maps for Diagnostic Applications.
Biosensors emerge as promising, cost-effective infectious disease diagnostics in resource-limited settings, requiring neither laboratory infrastructure nor specialized personnel. Surface plasmon resonance (SPR)-based biosensors remain preeminent for label-free, real-time analysis of biological interactions and kinetic parameter determination. Integrating Artificial Intelligence (AI), particularly self-organizing maps (SOMs), automates infection screening by projecting high-dimensional data onto topology-preserving 2D maps, offering advantages in diagnostic strategies by enabling efficient classification of infected vs healthy patients. This study presents an SPR biosensor with SOM analysis to enhance serodiagnosis of canine visceral leishmaniasis (CVL), a neglected tropical disease, whose delayed and inadequate detection in human and canine populations compromises effective disease control. The reaction kinetics of PQ20, a multiepitope chimeric protein with 20 B- and T-cell epitopes, with anti-PQ20 was evaluated. The proposed mechanism suggests two immunodominant epitopes of PQ20 through its reaction with polyclonal antibodies of Leishmania chagasi, presenting high initial association rates (ka1 = 2.4 × 105 L mol-1 s-1; kd1 = 5.5 × 10-4 L mol-1 s-1). The biosensor's diagnostic performance was evaluated, achieving a 5.1 nmol L-1 detection limit. SOM clustering indicated a higher specificity at shorter reaction times, supporting reduced diagnostic timelines (100 s) in accordance with kinetic evaluation. Finally, SOM-based data interpretation improved sensitivity and specificity compared to univariate analysis in raw serum, enhancing the assay's ability to classify samples in more complex media, in less than 15 min analysis time. Integrating multiepitope bioreceptors with AI-driven analysis offers rapid and label-free CVL surveillance, with broader applications for the management of this infectious disease.
期刊介绍:
ACS Sensors is a peer-reviewed research journal that focuses on the dissemination of new and original knowledge in the field of sensor science, particularly those that selectively sense chemical or biological species or processes. The journal covers a broad range of topics, including but not limited to biosensors, chemical sensors, gas sensors, intracellular sensors, single molecule sensors, cell chips, and microfluidic devices. It aims to publish articles that address conceptual advances in sensing technology applicable to various types of analytes or application papers that report on the use of existing sensing concepts in new ways or for new analytes.