使用深度卷积神经网络验证 NGS 数据中的遗传变异。

Validation of genetic variants from NGS data using deep convolutional neural networks.

机构信息

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center; Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR); Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.

出版信息

BMC Bioinformatics. 2023 Apr 20;24(1):158. doi: 10.1186/s12859-023-05255-7.

Abstract

Accurate somatic variant calling from next-generation sequencing data is one most important tasks in personalised cancer therapy. The sophistication of the available technologies is ever-increasing, yet, manual candidate refinement is still a necessary step in state-of-the-art processing pipelines. This limits reproducibility and introduces a bottleneck with respect to scalability. We demonstrate that the validation of genetic variants can be improved using a machine learning approach resting on a Convolutional Neural Network, trained using existing human annotation. In contrast to existing approaches, we introduce a way in which contextual data from sequencing tracks can be included into the automated assessment. A rigorous evaluation shows that the resulting model is robust and performs on par with trained researchers following published standard operating procedure.

摘要

从下一代测序数据中准确地调用体细胞变异是个性化癌症治疗中最重要的任务之一。现有的技术越来越复杂,但在最先进的处理管道中,手动候选物细化仍然是必要的步骤。这限制了可重复性,并引入了可扩展性方面的瓶颈。我们证明,使用基于卷积神经网络的机器学习方法可以提高遗传变异的验证,该方法使用现有的人工注释进行训练。与现有方法相比,我们引入了一种可以将测序轨道的上下文数据纳入自动评估的方法。严格的评估表明,所得到的模型是稳健的,并且可以与按照已发布的标准操作程序进行训练的研究人员相媲美。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f659/10116675/4df982ef6d9c/12859_2023_5255_Fig1_HTML.jpg

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