在 32,000 人的电子病历中,遗传性癫痫的临床特征先于诊断。

IF 6.6 1区 医学 Q1 GENETICS & HEREDITY
Peter D. Galer , Shridhar Parthasarathy , Julie Xian , Jillian L. McKee , Sarah M. Ruggiero , Shiva Ganesan , Michael C. Kaufman , Stacey R. Cohen , Scott Haag , Chen Chen , William K.S. Ojemann , Dan Kim , Olivia Wilmarth , Priya Vaidiswaran , Casey Sederman , Colin A. Ellis , Alexander K. Gonzalez , Christian M. Boßelmann , Dennis Lal , Rob Sederman , Ingo Helbig
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引用次数: 0

摘要

目的:早期基因诊断可指导对遗传性癫痫患者进行及时治疗。然而,大多数基因诊断是在发病后很长时间才做出的。我们旨在通过对电子病历(EMR)全文进行大规模分析,找出癫痫患者中提示基因诊断的早期临床特征:我们使用自然语言处理技术从 32,112 名儿童癫痫患者的 4,572,783 份临床记录中提取了 8,900 万条带有时间戳的标准化临床注释,其中包括 1,925 名已知或推测患有遗传性癫痫的患者。我们将这些特征用于训练随机森林模型,以预测 SCN1A 相关疾病和任何基因诊断:我们发现了 47,774 个临床特征与遗传病因的年龄相关性,中位数为分子诊断前 3.6 年。在我们队列中发现的所有 710 种遗传病因中,6-9 个月之间的神经发育差异使后来分子诊断的可能性增加了 5 倍(PC 结论:临床特征可预测遗传性癫痫的发生:在已知有精确治疗方法的情况下,可预测遗传性癫痫的临床特征比分子诊断早几年。通过自动EMR分析进行早期诊断,有可能为遗传性癫痫的早期靶向治疗策略提供帮助。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical signatures of genetic epilepsies precede diagnosis in electronic medical records of 32,000 individuals

Purpose

An early genetic diagnosis can guide the time-sensitive treatment of individuals with genetic epilepsies. However, most genetic diagnoses occur long after disease onset. We aimed to identify early clinical features suggestive of genetic diagnoses in individuals with epilepsy through large-scale analysis of full-text electronic medical records.

Methods

We extracted 89 million time-stamped standardized clinical annotations using Natural Language Processing from 4,572,783 clinical notes from 32,112 individuals with childhood epilepsy, including 1925 individuals with known or presumed genetic epilepsies. We applied these features to train random forest models to predict SCN1A-related disorders and any genetic diagnosis.

Results

We identified 47,774 age-dependent associations of clinical features with genetic etiologies a median of 3.6 years before molecular diagnosis. Across all 710 genetic etiologies identified in our cohort, neurodevelopmental differences between 6 to 9 months increased the likelihood of a later molecular diagnosis 5-fold (P < .0001, 95% CI = 3.55-7.42). A later diagnosis of SCN1A-related disorders (area under the curve [AUC] = 0.91) or an overall positive genetic diagnosis (AUC = 0.82) could be reliably predicted using random forest models.

Conclusion

Clinical features predictive of genetic epilepsies precede molecular diagnoses by up to several years in conditions with known precision treatments. An earlier diagnosis facilitated by automated electronic medical records analysis has the potential for earlier targeted therapeutic strategies in the genetic epilepsies.

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来源期刊
Genetics in Medicine
Genetics in Medicine 医学-遗传学
CiteScore
15.20
自引率
6.80%
发文量
857
审稿时长
1.3 weeks
期刊介绍: Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health. GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.
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