比较分析了基于模拟肿瘤样本的肿瘤含量估计方法,确定了它们对肿瘤全基因组测序中体细胞变异检测的影响。

IF 1.3 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Keiichi Ohshima, Masakuni Serizawa, Keiichi Hatakeyama, Sumiko Ohnami, Shumpei Ohnami, Akane Naruoka, Yasue Horiuchi, Akira Iizuka, Koji Maruyama, Yasuto Akiyama, Ken Yamaguchi
{"title":"比较分析了基于模拟肿瘤样本的肿瘤含量估计方法,确定了它们对肿瘤全基因组测序中体细胞变异检测的影响。","authors":"Takeshi Nagashima,&nbsp;Kenichi Urakami,&nbsp;Yuji Shimoda,&nbsp;Keiichi Ohshima,&nbsp;Masakuni Serizawa,&nbsp;Keiichi Hatakeyama,&nbsp;Sumiko Ohnami,&nbsp;Shumpei Ohnami,&nbsp;Akane Naruoka,&nbsp;Yasue Horiuchi,&nbsp;Akira Iizuka,&nbsp;Koji Maruyama,&nbsp;Yasuto Akiyama,&nbsp;Ken Yamaguchi","doi":"10.2220/biomedres.44.161","DOIUrl":null,"url":null,"abstract":"<p><p>Whole genome sequencing (WGS) in cancer genomics has become widespread with recent technological innovations, and the amount and types of information obtained from WGS are increasing rapidly. Appropriate interpretation of results is becoming increasingly important in clinical applications. This study aimed to evaluate the accuracy of tumor content estimation and its impact on somatic variant detection, using 100 simulated tumor samples covering 10-100% tumor content constructed from the sequencing data of cell line models. Extensive analysis revealed that the estimation results varied among computational analytical methods. Notably, there was a large discrepancy in low tumor content (≤ 30%). The reproducibility decreased in cases wherein chromosome-scale copy number changes were observed in normal cells. The minimum tumor content required to detect somatic alterations was estimated to be 10-30%. Identification of whole genome doubling was achieved with the lowest tumor content, followed by single nucleotide variation/insertion or deletion, structural variation, and copy number variation. Tumor content had a significantly higher impact on the false negatives than the false positives in variant calls. Results should be interpreted cautiously for samples wherein tumor content is a concern. These results can form the basis of developing important guidelines for evaluating cancer WGS.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparative analysis of tumor content estimation methods based on simu- lated tumor samples identified their impact on somatic variant detection in cancer whole genome sequencing.\",\"authors\":\"Takeshi Nagashima,&nbsp;Kenichi Urakami,&nbsp;Yuji Shimoda,&nbsp;Keiichi Ohshima,&nbsp;Masakuni Serizawa,&nbsp;Keiichi Hatakeyama,&nbsp;Sumiko Ohnami,&nbsp;Shumpei Ohnami,&nbsp;Akane Naruoka,&nbsp;Yasue Horiuchi,&nbsp;Akira Iizuka,&nbsp;Koji Maruyama,&nbsp;Yasuto Akiyama,&nbsp;Ken Yamaguchi\",\"doi\":\"10.2220/biomedres.44.161\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Whole genome sequencing (WGS) in cancer genomics has become widespread with recent technological innovations, and the amount and types of information obtained from WGS are increasing rapidly. Appropriate interpretation of results is becoming increasingly important in clinical applications. This study aimed to evaluate the accuracy of tumor content estimation and its impact on somatic variant detection, using 100 simulated tumor samples covering 10-100% tumor content constructed from the sequencing data of cell line models. Extensive analysis revealed that the estimation results varied among computational analytical methods. Notably, there was a large discrepancy in low tumor content (≤ 30%). The reproducibility decreased in cases wherein chromosome-scale copy number changes were observed in normal cells. The minimum tumor content required to detect somatic alterations was estimated to be 10-30%. Identification of whole genome doubling was achieved with the lowest tumor content, followed by single nucleotide variation/insertion or deletion, structural variation, and copy number variation. Tumor content had a significantly higher impact on the false negatives than the false positives in variant calls. Results should be interpreted cautiously for samples wherein tumor content is a concern. These results can form the basis of developing important guidelines for evaluating cancer WGS.</p>\",\"PeriodicalId\":9138,\"journal\":{\"name\":\"Biomedical Research-tokyo\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Research-tokyo\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2220/biomedres.44.161\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Research-tokyo","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2220/biomedres.44.161","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

随着近年来的技术创新,全基因组测序(WGS)在癌症基因组学中的应用越来越广泛,从WGS中获得的信息数量和类型也在迅速增加。结果的合理解释在临床应用中变得越来越重要。本研究旨在评估肿瘤含量估计的准确性及其对体细胞变异检测的影响,利用细胞系模型测序数据构建了100个模拟肿瘤样本,覆盖10-100%的肿瘤含量。广泛的分析表明,不同计算分析方法的估计结果存在差异。值得注意的是,低肿瘤含量(≤30%)差异较大。在正常细胞中观察到染色体规模拷贝数变化的情况下,可重复性降低。检测体细胞改变所需的最低肿瘤含量估计为10-30%。以最低的肿瘤含量鉴定全基因组加倍,其次是单核苷酸变异/插入或删除、结构变异和拷贝数变异。在变异呼叫中,肿瘤含量对假阴性的影响显著高于假阳性。结果应谨慎解释样本,其中肿瘤内容是一个问题。这些结果可以为制定评估癌症WGS的重要指南奠定基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative analysis of tumor content estimation methods based on simu- lated tumor samples identified their impact on somatic variant detection in cancer whole genome sequencing.

Whole genome sequencing (WGS) in cancer genomics has become widespread with recent technological innovations, and the amount and types of information obtained from WGS are increasing rapidly. Appropriate interpretation of results is becoming increasingly important in clinical applications. This study aimed to evaluate the accuracy of tumor content estimation and its impact on somatic variant detection, using 100 simulated tumor samples covering 10-100% tumor content constructed from the sequencing data of cell line models. Extensive analysis revealed that the estimation results varied among computational analytical methods. Notably, there was a large discrepancy in low tumor content (≤ 30%). The reproducibility decreased in cases wherein chromosome-scale copy number changes were observed in normal cells. The minimum tumor content required to detect somatic alterations was estimated to be 10-30%. Identification of whole genome doubling was achieved with the lowest tumor content, followed by single nucleotide variation/insertion or deletion, structural variation, and copy number variation. Tumor content had a significantly higher impact on the false negatives than the false positives in variant calls. Results should be interpreted cautiously for samples wherein tumor content is a concern. These results can form the basis of developing important guidelines for evaluating cancer WGS.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biomedical Research-tokyo
Biomedical Research-tokyo 医学-医学:研究与实验
CiteScore
2.40
自引率
0.00%
发文量
19
审稿时长
>12 weeks
期刊介绍: Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信