S Dennis Emmanuel, Dr. G Manikandan, Vilma Veronica, S. Hemalatha
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Our method is mainly based on machine learning (ML) techniques (support vector machines in particular) because of their ability to create multivariable models by learning patterns from complex data. Using novel feature selection and evaluation modalities we identified 5 novel panels of non-amyloid proteins with the potential to serve as biomarkers of early AD. In particular, we found that the combination of A2M, ApoE, BNP, Eot3, RAGE and SGOT may be a key biomarker profile of early disease. Disease detection models based on the identified panels achieved sensitivity (SN) > 80%, specificity (SP) > 70%, and area under receiver operating curve (AUC) of at least 0.80 at prodromal stage (with higher performance at later stages) of the disease. Existing ML models performed poorly in comparison at this stage of the disease suggesting that the underlying protein panels may not be suitable for early disease detection. 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引用次数: 0
摘要
基于淀粉样蛋白的阿尔茨海默病(AD)生物标记物和检测方法的成功开发是阿尔茨海默病诊断领域的一个重要里程碑。然而,目前仍存在两大局限性。基于淀粉样蛋白的诊断生物标记物和检测方法只能提供有关疾病过程的有限信息,而且它们无法在淀粉样蛋白-β在大脑中大量积聚之前识别出患病个体。本研究的目的是开发一种方法,以确定潜在的基于血液的非淀粉样蛋白生物标志物,用于早期AD检测。使用血液很有吸引力,因为它容易获得且相对便宜。我们的方法主要基于机器学习(ML)技术(尤其是支持向量机),因为它们能够通过从复杂数据中学习模式来创建多变量模型。利用新颖的特征选择和评估模式,我们确定了 5 组新的非淀粉样蛋白,它们有可能成为早期 AD 的生物标记物。特别是,我们发现 A2M、ApoE、BNP、Eot3、RAGE 和 SGOT 的组合可能是早期疾病的关键生物标志物特征。基于已识别面板的疾病检测模型在疾病前驱期(后期表现更佳)的灵敏度(SN)> 80%,特异度(SP)> 70%,接收器工作曲线下面积(AUC)至少为 0.80。相比之下,现有的 ML 模型在疾病的这一阶段表现不佳,这表明基础蛋白质面板可能不适合疾病的早期检测。我们的研究结果证明了使用非淀粉样蛋白生物标记物早期检测AD的可行性。
The successful development of amyloid-based biomarkers and tests for Alzheimer’s disease (AD) represents an important milestone in AD diagnosis. However, two major limitations remain. Amyloid-based diagnostic biomarkers and tests provide limited information about the disease process and they are unable to identify individuals with the disease before significant amyloid-beta accumulation in the brain develops. The objective in this study is to develop a method to identify potential blood-based non-amyloid biomarkers for early AD detection. The use of blood is attractive because it is accessible and relatively inexpensive. Our method is mainly based on machine learning (ML) techniques (support vector machines in particular) because of their ability to create multivariable models by learning patterns from complex data. Using novel feature selection and evaluation modalities we identified 5 novel panels of non-amyloid proteins with the potential to serve as biomarkers of early AD. In particular, we found that the combination of A2M, ApoE, BNP, Eot3, RAGE and SGOT may be a key biomarker profile of early disease. Disease detection models based on the identified panels achieved sensitivity (SN) > 80%, specificity (SP) > 70%, and area under receiver operating curve (AUC) of at least 0.80 at prodromal stage (with higher performance at later stages) of the disease. Existing ML models performed poorly in comparison at this stage of the disease suggesting that the underlying protein panels may not be suitable for early disease detection. Our results demonstrate the feasibility of early detection of AD using non-amyloid based biomarkers.