HerediVar and HerediClassify: tools for streamlining genetic variant classification in hereditary breast and ovarian cancer.

IF 3.8 3区医学 Q2 GENETICS & HEREDITY

Human Genomics Pub Date : 2025-07-04 DOI:10.1186/s40246-025-00787-w

Anna-Lena Katzke, Marvin Doebel, Jan Hauke, Gunnar Schmidt, Marc Sturm

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引用次数: 0

Abstract

Background: Multiple different evidence types as well as gene-specific variant classification guidelines need to be considered during the classification of variants, making the process complex. Therefore, tools that support variant classification by experts are urgently needed.

Methods: We present HerediVar a web application and HerediClassify a variant classification algorithm. The performance of HerediClassify was validated and compared to other variant classification tools. HerediClassify implements 19/28 variant classification criteria by the American College of Medical Genetics and gene-specific recommendations for ATM, BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53.

Results: HerediVar offers modular annotation services and allows for collaboration in the classification of variants. On the validation dataset, HerediClassify shows an average F1-Score of 93% across all criteria. HerediClassify outperforms other automated variant classification tools like vaRHC and Cancer SIGVAR.

Conclusion: In HerediVar and HerediClassify we present a powerful solution to support variant classification in HBOC. Through their modular design, HerediVar and HerediClassify are easily extendable to other use cases and human genetic diagnostics as a whole.

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遗传变异和遗传分类：简化遗传性乳腺癌和卵巢癌遗传变异分类的工具。

背景：在进行变异分类时，需要考虑多种不同的证据类型以及基因特异性的变异分类指南，使分类过程变得复杂。因此，迫切需要支持专家对变体进行分类的工具。方法：提出了一种web应用程序HerediVar和一种变体分类算法hericlass。对遗传分类的性能进行了验证，并与其他变体分类工具进行了比较。美国医学遗传学学院对ATM、BRCA1、BRCA2、CDH1、PALB2、PTEN和TP53的基因特异性推荐采用了19/28个变异分类标准。结果：HerediVar提供模块化注释服务，并允许在变体分类中进行协作。在验证数据集上，遗传分类显示所有标准的平均F1-Score为93%。遗传分类优于其他自动变异分类工具，如vaRHC和癌症SIGVAR。结论：在HerediVar和hericlassiy中，我们提供了一个支持HBOC变异分类的强大解决方案。通过模块化设计，HerediVar和hericlassiy可以很容易地扩展到其他用例和人类遗传诊断。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.