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基于血浆分析的用于鉴定脑淀粉样蛋白沉积的适体标志物的适体文库的可重现方法。

A reproducible approach for the use of aptamer libraries for the identification of Aptamarkers for brain amyloid deposition based on plasma analysis.

机构信息

NeoVentures Biotechnology Europe SAS, Villejuif Bio Park, Villejuif, France.

出版信息

PLoS One. 2024 Aug 27;19(8):e0307678. doi: 10.1371/journal.pone.0307678. eCollection 2024.

DOI:10.1371/journal.pone.0307678
PMID:39190656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11349097/
Abstract

An approach for the agnostic identification and validation of aptamers for the prediction of a medical state from plasma analysis is presented in application to a key risk factor for Alzheimer's disease. brain amyloid deposition. This method involved the use of a newly designed aptamer library with sixteen random nucleotides interspersed with fixed sequences called a Neomer library. The Neomer library approach enables the direct application of the same starting library on multiple plasma samples, without the requirement for pre-enrichment associated with the traditional approach. Eight aptamers were identified as a result of the selection process and screened across 390 plasma samples by qPCR assay. Results were analysed using multiple machine learning algorithms from the Scikit-learn package along with clinical variables including cognitive status, age and sex to create predictive models. An Extra Trees Classifier model provided the highest predictive power. The Neomer approach resulted in a sensitivity of 0.88. specificity of 0.76. and AUC of 0.79. The only clinical variables that were included in the model were age and sex. We conclude that the Neomer approach represents a clear improvement for the agnostic identification of aptamers (Aptamarkers) that bind to unknown biomarkers of a medical state.

摘要

提出了一种从血浆分析中预测医学状态的未知适体的识别和验证方法,应用于阿尔茨海默病的关键风险因素——脑淀粉样蛋白沉积。该方法涉及使用新设计的带有十六个随机核苷酸的适体文库,这些核苷酸与称为 Neomer 文库的固定序列交错。Neomer 文库方法能够在多个血浆样本上直接应用相同的起始文库,而无需传统方法所需的预富集。通过 qPCR 分析筛选了 390 个血浆样本,共鉴定出 8 个适体。结果使用来自 Scikit-learn 包的多种机器学习算法以及包括认知状态、年龄和性别在内的临床变量进行分析,以创建预测模型。Extra Trees 分类器模型提供了最高的预测能力。Neomer 方法的灵敏度为 0.88,特异性为 0.76,AUC 为 0.79。纳入模型的唯一临床变量是年龄和性别。我们得出结论,Neomer 方法代表了一种用于识别与医学状态未知生物标志物结合的适体(Aptamarkers)的明确改进方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/3a78d2a60016/pone.0307678.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/ee79da8df80e/pone.0307678.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/8ed4480888a6/pone.0307678.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/d7eb4694fa4b/pone.0307678.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/fb517d4ed816/pone.0307678.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/26454f26e552/pone.0307678.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/3a78d2a60016/pone.0307678.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/ee79da8df80e/pone.0307678.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/8ed4480888a6/pone.0307678.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/d7eb4694fa4b/pone.0307678.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/fb517d4ed816/pone.0307678.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/26454f26e552/pone.0307678.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9070/11349097/3a78d2a60016/pone.0307678.g006.jpg

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