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基于深度学习的抗水通道蛋白4抗体视神经脊髓炎谱系障碍复发预测

Deep learning-based relapse prediction of neuromyelitis optica spectrum disorder with anti-aquaporin-4 antibody.

作者信息

Wang Liang, Du Lei, Li Qinying, Li Fang, Wang Bei, Zhao Yuanqi, Meng Qiang, Li Wenyu, Pan Juyuan, Xia Junhui, Wu Shitao, Yang Jie, Li Heng, Ma Jianhua, ZhangBao Jingzi, Huang Wenjuan, Chang Xuechun, Tan Hongmei, Yu Jian, Zhou Lei, Lu Chuanzhen, Wang Min, Dong Qiang, Lu Jiahong, Zhao Chongbo, Quan Chao

机构信息

Department of Neurology, Huashan Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

National Center for Neurological Disorders (NCND), Shanghai, China.

出版信息

Front Neurol. 2022 Aug 5;13:947974. doi: 10.3389/fneur.2022.947974. eCollection 2022.

Abstract

OBJECTIVE

We previously identified the independent predictors of recurrent relapse in neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin-4 antibody (AQP4-ab) and designed a nomogram to estimate the 1- and 2-year relapse-free probability, using the Cox proportional hazard (Cox-PH) model, assuming that the risk of relapse had a linear correlation with clinical variables. However, whether the linear assumption fits real disease tragedy is unknown. We aimed to employ deep learning and machine learning to develop a novel prediction model of relapse in patients with NMOSD and compare the performance with the conventional Cox-PH model.

METHODS

This retrospective cohort study included patients with NMOSD with AQP4-ab in 10 study centers. In this study, 1,135 treatment episodes from 358 patients in Huashan Hospital were employed as the training set while 213 treatment episodes from 92 patients in nine other research centers as the validation set. We compared five models with added variables of gender, AQP4-ab titer, previous attack under the same therapy, EDSS score at treatment initiation, maintenance therapy, age at treatment initiation, disease duration, the phenotype of the most recent attack, and annualized relapse rate (ARR) of the most recent year by concordance index (C-index): conventional Cox-PH, random survival forest (RSF), LogisticHazard, DeepHit, and DeepSurv.

RESULTS

When including all variables, RSF outperformed the C-index in the training set (0.739), followed by DeepHit (0.737), LogisticHazard (0.722), DeepSurv (0.698), and Cox-PH (0.679) models. As for the validation set, the C-index of LogisticHazard outperformed the other models (0.718), followed by DeepHit (0.704), DeepSurv (0.698), RSF (0.685), and Cox-PH (0.651) models. Maintenance therapy was calculated to be the most important variable for relapse prediction.

CONCLUSION

This study confirmed the superiority of deep learning to design a prediction model of relapse in patients with AQP4-ab-positive NMOSD, with the LogisticHazard model showing the best predictive power in validation.

摘要

目的

我们之前确定了抗水通道蛋白4抗体(AQP4-ab)阳性的视神经脊髓炎谱系障碍(NMOSD)复发的独立预测因素,并使用Cox比例风险(Cox-PH)模型设计了一个列线图来估计1年和2年无复发概率,假设复发风险与临床变量存在线性相关性。然而,这种线性假设是否符合实际疾病情况尚不清楚。我们旨在运用深度学习和机器学习开发一种NMOSD患者复发的新型预测模型,并将其性能与传统的Cox-PH模型进行比较。

方法

这项回顾性队列研究纳入了10个研究中心的AQP4-ab阳性NMOSD患者。在本研究中,来自华山医院358例患者的1135个治疗阶段被用作训练集,而来自其他9个研究中心92例患者的213个治疗阶段作为验证集。我们通过一致性指数(C-index)比较了五个添加了性别、AQP4-ab滴度、相同治疗下的既往发作、治疗开始时的扩展残疾状态量表(EDSS)评分、维持治疗、治疗开始时的年龄、病程、最近一次发作的表型以及最近一年的年化复发率(ARR)等变量的模型:传统的Cox-PH模型、随机生存森林(RSF)模型、LogisticHazard模型、DeepHit模型和DeepSurv模型。

结果

当纳入所有变量时,RSF在训练集中的C-index表现最佳(0.739),其次是DeepHit(0.737)、LogisticHazard(0.722)、DeepSurv(0.698)和Cox-PH(0.679)模型。在验证集中,LogisticHazard的C-index优于其他模型(0.718),其次是DeepHit(0.704)、DeepSurv(0.698)、RSF(0.685)和Cox-PH(0.651)模型。维持治疗被计算为复发预测中最重要的变量。

结论

本研究证实了深度学习在设计AQP4-ab阳性NMOSD患者复发预测模型方面的优越性,其中LogisticHazard模型在验证中显示出最佳预测能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af0/9389264/f086223bce99/fneur-13-947974-g0001.jpg

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