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靶向下一代测序和深度学习应用检测染色体结构变异。

Detection of chromosome structural variation by targeted next-generation sequencing and a deep learning application.

机构信息

Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Center for Cancer Genome Discovery, Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

出版信息

Sci Rep. 2019 Mar 6;9(1):3644. doi: 10.1038/s41598-019-40364-5.


DOI:10.1038/s41598-019-40364-5
PMID:30842562
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6403216/
Abstract

Molecular testing is increasingly important in cancer diagnosis. Targeted next generation sequencing (NGS) is widely accepted method but structural variation (SV) detection by targeted NGS remains challenging. In the brain tumor, identification of molecular alterations, including 1p/19q co-deletion, is essential for accurate glial tumor classification. Hence, we used targeted NGS to detect 1p/19q co-deletion using a newly developed deep learning (DL) model in 61 tumors, including 19 oligodendroglial tumors. An ensemble 1-dimentional convolution neural network was developed and used to detect the 1p/19q co-deletion. External validation was performed using 427 low-grade glial tumors from The Cancer Genome Atlas (TCGA). Manual review of the copy number plot from the targeted NGS identified the 1p/19q co-deletion in all 19 oligodendroglial tumors. Our DL model also perfectly detected the 1p/19q co-deletion (area under the curve, AUC = 1) in the testing set, and yielded reproducible results (AUC = 0.9652) in the validation set (n = 427), although the validation data were generated on a completely different platform (SNP Array 6.0 platform). In conclusion, targeted NGS using a cancer gene panel is a promising approach for classifying glial tumors, and DL can be successfully integrated for the SV detection in NGS data.

摘要

分子检测在癌症诊断中越来越重要。靶向下一代测序(NGS)是一种广泛接受的方法,但靶向 NGS 的结构变异(SV)检测仍然具有挑战性。在脑肿瘤中,鉴定分子改变,包括 1p/19q 共缺失,对于准确的神经胶质瘤分类至关重要。因此,我们使用靶向 NGS 检测 61 个肿瘤中的 1p/19q 共缺失,包括 19 个少突胶质细胞瘤。我们开发了一个集成的一维卷积神经网络,并用于检测 1p/19q 共缺失。使用来自癌症基因组图谱(TCGA)的 427 个低级别神经胶质瘤进行外部验证。通过靶向 NGS 的拷贝数图谱进行手动审查,鉴定了所有 19 个少突胶质细胞瘤中的 1p/19q 共缺失。我们的 DL 模型还在测试集中完美地检测到 1p/19q 共缺失(曲线下面积,AUC=1),并在验证集(n=427)中产生可重复的结果(AUC=0.9652),尽管验证数据是在完全不同的平台(SNP 阵列 6.0 平台)上生成的。总之,使用癌症基因panel 的靶向 NGS 是一种有前途的胶质肿瘤分类方法,并且可以成功地将 DL 集成到 NGS 数据的 SV 检测中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/17c916ad89c2/41598_2019_40364_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/ddd61a3058c6/41598_2019_40364_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/0c119a234de6/41598_2019_40364_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/fcba06c3bb27/41598_2019_40364_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/17c916ad89c2/41598_2019_40364_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/ddd61a3058c6/41598_2019_40364_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/0c119a234de6/41598_2019_40364_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/fcba06c3bb27/41598_2019_40364_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/6403216/17c916ad89c2/41598_2019_40364_Fig4_HTML.jpg

相似文献

[1]
Detection of chromosome structural variation by targeted next-generation sequencing and a deep learning application.

Sci Rep. 2019-3-6

[2]
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[3]
Alpha-internexin and altered CIC expression as a supportive diagnostic marker for oligodendroglial tumors with the 1p/19q co-deletion.

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[4]
[Diagnostic and prognostic roles of loss of CIC protein expression in oligodendroglial tumors].

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[5]
Eighty percent survival rate at 15 years for 1p/19q co-deleted oligodendroglioma treated with upfront chemotherapy irrespective of tumor grade.

J Neurooncol. 2018-12-18

[6]
Molecular analysis of chromosome 1, 10 and 19 abnormalities in human oligodendroglial tumors: relationship between frequency of LOH grade, age and gender.

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[7]
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[8]
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Oncotarget. 2016-10-4

[9]
Contribution of 1p, 19q, 9p and 10q Automated Analysis by FISH to the Diagnosis and Prognosis of Oligodendroglial Tumors According to WHO 2016 Guidelines.

PLoS One. 2016-12-28

[10]
Regional specificity of 1p/19q co-deletion combined with radiological features for predicting the survival outcomes of anaplastic oligodendroglial tumor patients.

J Neurooncol. 2017-12-11

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[2]
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[3]
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[4]
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[5]
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Acta Neuropathol Commun. 2022-11-17

[6]
From molecules to genomic variations: Accelerating genome analysis via intelligent algorithms and architectures.

Comput Struct Biotechnol J. 2022-8-18

[7]
Towards accurate and reliable resolution of structural variants for clinical diagnosis.

Genome Biol. 2022-3-3

[8]
Diagnostic test accuracy and cost-effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma.

Cochrane Database Syst Rev. 2022-3-2

[9]
Diagnostic accuracy of 1p/19q codeletion tests in oligodendroglioma: A comprehensive meta-analysis based on a Cochrane systematic review.

Neuropathol Appl Neurobiol. 2022-6

[10]
Machine learning random forest for predicting oncosomatic variant NGS analysis.

Sci Rep. 2021-11-8

本文引用的文献

[1]
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