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基于外周血基因表达的精神分裂症诊断的机器学习算法。

The machine learning algorithm for the diagnosis of schizophrenia on the basis of gene expression in peripheral blood.

机构信息

School of Public Health of Guangxi Medical University, Nanning, Guangxi, China.

School of Public Health of Guangxi Medical University, Nanning, Guangxi, China.

出版信息

Neurosci Lett. 2021 Feb 6;745:135596. doi: 10.1016/j.neulet.2020.135596. Epub 2020 Dec 24.

DOI:10.1016/j.neulet.2020.135596
PMID:33359735
Abstract

BACKGROUND

Schizophrenia (SCZ) is a highly heritable mental disorder with a substantial disease burden. Machine learning (ML) method can be used to identify individuals with SCZ on the basis of blood gene expression data with high accuracy.

METHODS

This study aimed to differentiate patients with SCZ from healthy individuals by using the messenger RNA expression level in peripheral blood of 48 patients with SCZ and 50 controls via ML algorithms, namely, artificial neural networks, extreme gradient boosting, support vector machine (SVM), decision tree, and random forest. The expression of six mRNAs was detected using quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

The relative expression levels of GNAI1 (P < 0.001), PRKCA (P < 0.001), and PRKCB (P = 0.021) increased in the SCZ group, whereas those of FYN (P < 0.001), LYN (P = 0.022), and YWHAZ (P < 0.001) decreased in the SCZ group. We generated models with various combinations of genes based on five ML algorithms. The SVM model with six factors (GNAI1, FYN, PRKCA, YWHAZ, PRKCB, and LYN genes) was the best model for distinguishing patients with SCZ from healthy individuals (AUC = 0.993, sensitivity = 1.000, specificity = 0.895, and Youden index = 0.895).

CONCLUSIONS

This study suggested that the combination of genes using the ML method is better than the use of a single gene to discriminate patients with SCZ from healthy individuals. The combination of GNAI1, FYN, PRKCA, YWHAZ, PRKCB, and LYN under the SVM model can be used as a diagnostic biomarker for SCZ.

摘要

背景

精神分裂症(SCZ)是一种具有高度遗传性且疾病负担较重的精神障碍。机器学习(ML)方法可用于根据精神分裂症患者的外周血基因表达数据准确识别患者。

方法

本研究旨在通过 ML 算法(包括人工神经网络、极端梯度提升、支持向量机(SVM)、决策树和随机森林),识别 48 例精神分裂症患者和 50 例对照者外周血中的信使 RNA 表达水平,以区分精神分裂症患者和健康对照者。采用实时荧光定量聚合酶链反应(qRT-PCR)检测 6 个 mRNAs 的表达。

结果

SCZ 组中 GNAI1(P<0.001)、PRKCA(P<0.001)和 PRKCB(P=0.021)的相对表达水平升高,而 FYN(P<0.001)、LYN(P=0.022)和 YWHAZ(P<0.001)的相对表达水平降低。我们基于 5 种 ML 算法生成了各种基因组合的模型。基于 6 个因素(GNAI1、FYN、PRKCA、YWHAZ、PRKCB 和 LYN 基因)的 SVM 模型是区分精神分裂症患者和健康对照者的最佳模型(AUC=0.993,灵敏度=1.000,特异性=0.895,约登指数=0.895)。

结论

本研究提示,ML 方法联合使用基因优于单一基因用于区分精神分裂症患者和健康对照者。SVM 模型下 GNAI1、FYN、PRKCA、YWHAZ、PRKCB 和 LYN 联合可作为精神分裂症的诊断生物标志物。

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