A Clinically Annotated Transcriptomic Atlas of Nervous System Tumors.

IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY
Chi H Le, Ajai K Nelson, Adam J Berrones, Janki R Naidugari, Robert P Naftel, Eyas M Hattab, Brian J Williams, Akshitkumar M Mistry
{"title":"A Clinically Annotated Transcriptomic Atlas of Nervous System Tumors.","authors":"Chi H Le, Ajai K Nelson, Adam J Berrones, Janki R Naidugari, Robert P Naftel, Eyas M Hattab, Brian J Williams, Akshitkumar M Mistry","doi":"10.1093/neuonc/noaf130","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>While DNA methylation signatures are distinct across nervous system neoplasms, it has not been comprehensively demonstrated whether transcriptomic signatures exhibit similar uniqueness. Additionally, no large-scale dataset for comparative gene expression analyses exists. This study addresses these knowledge and resource gaps.</p><p><strong>Methods: </strong>We compiled and harmonized raw transcriptomic and clinical data for neoplastic (n=5,402) and non-neoplastic (n=1,973) nervous system samples from publicly available sources, all profiled on the same microarray platform. After adjusting for surrogate variable effects ('batch effects'), machine learning methods were used to visualize, cluster, and reclassify samples with uncertain diagnoses (n=2,225).</p><p><strong>Results: </strong>We generated the largest clinically annotated transcriptomic atlas of nervous system tumors to date. Sample clustering was primarily driven by diagnosis. We show the utility of the atlas by refining the transcriptional subtypes of pheochromocytoma and paraganglioma (PH/PG), revealing six robust subtypes (Neuronal, Vascular, Metabolic, Steroidal, Developmental, Indeterminate), which were independently validated using TCGA RNA-seq data and that correlated with specific mutational signatures and clinical behaviors of these tumors.</p><p><strong>Conclusions: </strong>Like bulk DNA methylation, we demonstrate that bulk transcriptomic signatures are distinct across the diagnostic spectrum of nervous system neoplasms. Our atlas' broad coverage of diagnoses, including rarely studied entities, spans all ages and includes individuals from diverse geographical regions, enhancing its utility for comprehensive and robust comparative gene expression analyses, as exemplified by our PH/PG analyses. For access visit http://kdph.shinyapps.io/atlas/ or https://github.com/axitamm/BrainTumorAtlas.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/neuonc/noaf130","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: While DNA methylation signatures are distinct across nervous system neoplasms, it has not been comprehensively demonstrated whether transcriptomic signatures exhibit similar uniqueness. Additionally, no large-scale dataset for comparative gene expression analyses exists. This study addresses these knowledge and resource gaps.

Methods: We compiled and harmonized raw transcriptomic and clinical data for neoplastic (n=5,402) and non-neoplastic (n=1,973) nervous system samples from publicly available sources, all profiled on the same microarray platform. After adjusting for surrogate variable effects ('batch effects'), machine learning methods were used to visualize, cluster, and reclassify samples with uncertain diagnoses (n=2,225).

Results: We generated the largest clinically annotated transcriptomic atlas of nervous system tumors to date. Sample clustering was primarily driven by diagnosis. We show the utility of the atlas by refining the transcriptional subtypes of pheochromocytoma and paraganglioma (PH/PG), revealing six robust subtypes (Neuronal, Vascular, Metabolic, Steroidal, Developmental, Indeterminate), which were independently validated using TCGA RNA-seq data and that correlated with specific mutational signatures and clinical behaviors of these tumors.

Conclusions: Like bulk DNA methylation, we demonstrate that bulk transcriptomic signatures are distinct across the diagnostic spectrum of nervous system neoplasms. Our atlas' broad coverage of diagnoses, including rarely studied entities, spans all ages and includes individuals from diverse geographical regions, enhancing its utility for comprehensive and robust comparative gene expression analyses, as exemplified by our PH/PG analyses. For access visit http://kdph.shinyapps.io/atlas/ or https://github.com/axitamm/BrainTumorAtlas.

神经系统肿瘤临床注释转录组图谱。
背景:虽然DNA甲基化特征在神经系统肿瘤中是不同的,但转录组特征是否具有类似的独特性尚未得到全面证明。此外,还没有大规模的比较基因表达分析数据集。本研究解决了这些知识和资源差距。方法:我们汇编并统一了来自公开来源的肿瘤(n= 5402)和非肿瘤(n= 1973)神经系统样本的原始转录组学和临床数据,所有样本都在相同的微阵列平台上进行了分析。在调整代理变量效应(“批处理效应”)后,使用机器学习方法对诊断不确定的样本进行可视化、聚类和重新分类(n= 2225)。结果:我们生成了迄今为止最大的临床注释神经系统肿瘤转录组图谱。样本聚类主要由诊断驱动。我们通过细化嗜铬细胞瘤和副神经节瘤(PH/PG)的转录亚型来展示图谱的效用,揭示了六种强大的亚型(神经元型、血管型、代谢型、甾体型、发育型、不确定型),这些亚型使用TCGA RNA-seq数据独立验证,并且与这些肿瘤的特定突变特征和临床行为相关。结论:与大量DNA甲基化一样,我们证明了大量转录组特征在神经系统肿瘤的诊断谱中是不同的。我们的图谱涵盖了广泛的诊断,包括很少研究的实体,涵盖了所有年龄段,包括来自不同地理区域的个体,增强了其在全面和稳健的比较基因表达分析中的实用性,例如我们的PH/PG分析。访问网址:http://kdph.shinyapps.io/atlas/或https://github.com/axitamm/BrainTumorAtlas。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Neuro-oncology
Neuro-oncology 医学-临床神经学
CiteScore
27.20
自引率
6.30%
发文量
1434
审稿时长
3-8 weeks
期刊介绍: Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field. The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
×
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:604180095
Book学术官方微信