TY - JOUR
T1 - DNA methylation-based epigenetic signatures predict somatic genomic alterations in gliomas
AU - Yang, Jie
AU - Wang, Qianghu
AU - Zhang, Ze Yan
AU - Long, Lihong
AU - Ezhilarasan, Ravesanker
AU - Karp, Jerome M.
AU - Tsirigos, Aristotelis
AU - Snuderl, Matija
AU - Wiestler, Benedikt
AU - Wick, Wolfgang
AU - Miao, Yinsen
AU - Huse, Jason T.
AU - Sulman, Erik P.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Molecular classification has improved diagnosis and treatment for patients with malignant gliomas. However, classification has relied on individual assays that are both costly and slow, leading to frequent delays in treatment. Here, we propose the use of DNA methylation, as an emerging clinical diagnostic platform, to classify gliomas based on major genomic alterations and provide insight into subtype characteristics. We show that using machine learning models, DNA methylation signatures can accurately predict somatic alterations and show improvement over existing classifiers. The established Unified Diagnostic Pipeline (UniD) we develop is rapid and cost-effective for genomic alterations and gene expression subtypes diagnostic at early clinical phase and improves over individual assays currently in clinical use. The significant relationship between genetic alteration and epigenetic signature indicates broad applicability of our approach to other malignancies.
AB - Molecular classification has improved diagnosis and treatment for patients with malignant gliomas. However, classification has relied on individual assays that are both costly and slow, leading to frequent delays in treatment. Here, we propose the use of DNA methylation, as an emerging clinical diagnostic platform, to classify gliomas based on major genomic alterations and provide insight into subtype characteristics. We show that using machine learning models, DNA methylation signatures can accurately predict somatic alterations and show improvement over existing classifiers. The established Unified Diagnostic Pipeline (UniD) we develop is rapid and cost-effective for genomic alterations and gene expression subtypes diagnostic at early clinical phase and improves over individual assays currently in clinical use. The significant relationship between genetic alteration and epigenetic signature indicates broad applicability of our approach to other malignancies.
UR - http://www.scopus.com/inward/record.url?scp=85135147761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85135147761&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-31827-x
DO - 10.1038/s41467-022-31827-x
M3 - Article
C2 - 35906213
AN - SCOPUS:85135147761
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4410
ER -