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一种用于高维事件时间预测的机器学习方法及其在 ABIRISK 队列中生物疗法免疫原性的应用。

A Machine Learning Approach for High-Dimensional Time-to-Event Prediction With Application to Immunogenicity of Biotherapies in the ABIRISK Cohort.

机构信息

Research Center, Ste-Justine Hospital, Montreal, QC, Canada.

UMR 1018, INSERM, CESP, Paris-Saclay University Faculty of Medicine, Paul-Brousse Hospital, Villejuif, France.

出版信息

Front Immunol. 2020 Apr 7;11:608. doi: 10.3389/fimmu.2020.00608. eCollection 2020.

DOI:10.3389/fimmu.2020.00608
PMID:32318076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7154163/
Abstract

Predicting immunogenicity for biotherapies using patient and drug-related factors represents nowadays a challenging issue. With the growing ability to collect massive amount of data, machine learning algorithms can provide efficient predictive tools. From the bio-clinical data collected in the multi-cohort of autoimmune diseases treated with biotherapies from the ABIRISK consortium, we evaluated the predictive power of a custom-built random survival forest for predicting the occurrence of anti-drug antibodies. This procedure takes into account the existence of a population composed of immune-reactive and immune-tolerant subjects as well as the existence of a tiny expected proportion of relevant predictive variables. The practical application to the ABIRISK cohort shows that this approach provides a good predictive accuracy that outperforms the classical survival random forest procedure. Moreover, the individual predicted probabilities allow to separate high and low risk group of patients. To our best knowledge, this is the first study to evaluate the use of machine learning procedures to predict biotherapy immunogenicity based on bioclinical information. It seems that such approach may have potential to provide useful information for the clinical practice of stratifying patients before receiving a biotherapy.

摘要

使用患者和药物相关因素预测生物疗法的免疫原性是当今的一个具有挑战性的问题。随着收集大量数据的能力不断增强,机器学习算法可以提供有效的预测工具。我们从 ABIRISK 联盟治疗自身免疫性疾病的多队列中收集的生物临床数据中,评估了自定义随机生存森林在预测抗药物抗体发生方面的预测能力。该过程考虑到了由免疫反应性和免疫耐受性受试者组成的人群的存在,以及存在一小部分相关预测变量的预期比例。该方法在 ABIRISK 队列中的实际应用表明,该方法提供了良好的预测准确性,优于经典的生存随机森林方法。此外,个体预测概率可以将患者分为高风险和低风险组。据我们所知,这是第一项基于生物临床信息评估使用机器学习程序预测生物疗法免疫原性的研究。这种方法似乎有可能为生物疗法治疗前对患者进行分层的临床实践提供有用信息。

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