[Feasibility study on the use of peripheral blood differentially expressed genes for objective classification of chronic subjective tinnitus: a case study on high-frequency tinnitus].

Z C Li, B X Fang, J Xie, X Y Wang, J S Zhou, X L Zeng
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Abstract

Objective: To explore the feasibility of constructing an objective tinnitus subtype model based on peripheral blood differentially expressed genes (DEGs) using a combination of Weighted Gene Co-expression Network Analysis (WGCNA) and Random Forest algorithm (RF). Methods: From October 2019 to June 2020, peripheral blood DEGs were obtained from 37 patients (from the Third Affiliated Hospital of Sun Yat-sen University)with chronic subjective high-frequency tinnitus (21 unbothersome type, 16 bothersome type) and 20 healthy volunteers through high-throughput sequencing. WGCNA was used to construct gene modules with different expression patterns and analyze their relationships with tinnitus characteristics. Subsequently, RF was employed to build subtype models, which were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, and F1-score. Results: A total of 12 351 intergroup DEGs were divided into 9 gene modules. Among them, MEblue, MEgreen, and MEbrown showed significant negative correlations with the healthy volunteer group, while MEpink showed a significant positive correlation with the tinnitus distress group. The "Tinnitus vs. Normal" and "Compensatory vs. Decompensatory" subtype models, based on MEblue and MEpink respectively, both had AUCs greater than 0.80, accuracies above 90%, and F1-scores above 0.90, indicating good performance. Conclusions: Peripheral blood DEGs are potential biological indicators for objective classification of subjective tinnitus. The combined application of WGCNA and the Random Forest algorithm should be a viable approach to constructing an objective tinnitus subtype model. However, further exploration and refinement are needed to validate the model's generalizability, cross-dataset performance, and algorithm optimization.

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[利用外周血差异表达基因对慢性主观性耳鸣进行客观分类的可行性研究:高频耳鸣案例研究]。
目的利用加权基因共表达网络分析(WGCNA)和随机森林算法(RF),探索基于外周血差异表达基因(DEGs)构建客观耳鸣亚型模型的可行性。研究方法2019年10月至2020年6月,通过高通量测序获得了37名慢性主观高频耳鸣患者(中山大学附属第三医院)(21名非困扰型,16名困扰型)和20名健康志愿者的外周血DEGs。利用 WGCNA 构建了不同表达模式的基因模块,并分析了它们与耳鸣特征的关系。随后,利用RF建立亚型模型,并通过接收者操作特征曲线下面积(AUC)、准确率和F1-score进行评估。结果共有 12 351 个组间 DEGs 被划分为 9 个基因模块。其中,MEblue、MEgreen和MEbrown与健康志愿者组呈显著负相关,而MEpink与耳鸣困扰组呈显著正相关。分别基于 MEblue 和 MEpink 的 "耳鸣 vs. 正常 "和 "补偿 vs. 非补偿 "亚型模型的 AUC 均大于 0.80,准确率超过 90%,F1 分数超过 0.90,表明其性能良好。结论外周血 DEGs 是对主观耳鸣进行客观分类的潜在生物指标。结合应用 WGCNA 和随机森林算法应该是构建客观耳鸣亚型模型的可行方法。不过,还需要进一步探索和完善,以验证模型的通用性、跨数据集性能和算法优化。
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