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MethylNet:一种用于 DNA 甲基化分析的自动化和模块化深度学习方法。

MethylNet: an automated and modular deep learning approach for DNA methylation analysis.

机构信息

Program in Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.

Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.

出版信息

BMC Bioinformatics. 2020 Mar 17;21(1):108. doi: 10.1186/s12859-020-3443-8.


DOI:10.1186/s12859-020-3443-8
PMID:32183722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7076991/
Abstract

BACKGROUND: DNA methylation (DNAm) is an epigenetic regulator of gene expression programs that can be altered by environmental exposures, aging, and in pathogenesis. Traditional analyses that associate DNAm alterations with phenotypes suffer from multiple hypothesis testing and multi-collinearity due to the high-dimensional, continuous, interacting and non-linear nature of the data. Deep learning analyses have shown much promise to study disease heterogeneity. DNAm deep learning approaches have not yet been formalized into user-friendly frameworks for execution, training, and interpreting models. Here, we describe MethylNet, a DNAm deep learning method that can construct embeddings, make predictions, generate new data, and uncover unknown heterogeneity with minimal user supervision. RESULTS: The results of our experiments indicate that MethylNet can study cellular differences, grasp higher order information of cancer sub-types, estimate age and capture factors associated with smoking in concordance with known differences. CONCLUSION: The ability of MethylNet to capture nonlinear interactions presents an opportunity for further study of unknown disease, cellular heterogeneity and aging processes.

摘要

背景:DNA 甲基化(DNAm)是一种基因表达程序的表观遗传调控因子,它可以通过环境暴露、衰老和发病机制发生改变。由于数据的高维性、连续性、相互作用和非线性,与 DNAm 改变相关联的表型的传统分析受到多重假设检验和多重共线性的影响。深度学习分析在研究疾病异质性方面显示出很大的前景。DNAm 深度学习方法尚未形式化为用户友好的执行、训练和解释模型的框架。在这里,我们描述了 MethylNet,这是一种 DNAm 深度学习方法,它可以在最小的用户监督下构建嵌入、进行预测、生成新数据和揭示未知的异质性。

结果:我们的实验结果表明,MethylNet 可以研究细胞差异,掌握癌症亚型的更高阶信息,估计年龄,并捕捉与吸烟相关的因素,与已知的差异一致。

结论:MethylNet 捕捉非线性相互作用的能力为进一步研究未知疾病、细胞异质性和衰老过程提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/655cfcfa6224/12859_2020_3443_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/45f300ac1ca4/12859_2020_3443_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/2955ca4f30e6/12859_2020_3443_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/4fab426eb6bd/12859_2020_3443_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/655cfcfa6224/12859_2020_3443_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/45f300ac1ca4/12859_2020_3443_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/2955ca4f30e6/12859_2020_3443_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/4fab426eb6bd/12859_2020_3443_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2191/7076991/655cfcfa6224/12859_2020_3443_Fig4_HTML.jpg

相似文献

[1]
MethylNet: an automated and modular deep learning approach for DNA methylation analysis.

BMC Bioinformatics. 2020-3-17

[2]
MethylSPWNet and MethylCapsNet: Biologically Motivated Organization of DNAm Neural Networks, Inspired by Capsule Networks.

NPJ Syst Biol Appl. 2021-8-20

[3]
Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium MethylationEPIC BeadChip array.

Clin Epigenetics. 2018-10-16

[4]
Estimating breast tissue-specific DNA methylation age using next-generation sequencing data.

Clin Epigenetics. 2020-3-12

[5]
The influences of DNA methylation and epigenetic clocks, on metabolic disease, in middle-aged Koreans.

Clin Epigenetics. 2020-10-15

[6]
Characterization of age signatures of DNA methylation in normal and cancer tissues from multiple studies.

BMC Genomics. 2014-11-19

[7]
pwrEWAS: a user-friendly tool for comprehensive power estimation for epigenome wide association studies (EWAS).

BMC Bioinformatics. 2019-4-29

[8]
Chronological age prediction based on DNA methylation: Massive parallel sequencing and random forest regression.

Forensic Sci Int Genet. 2017-11

[9]
Human aging DNA methylation signatures are conserved but accelerated in cultured fibroblasts.

Epigenetics. 2019-6-12

[10]
Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context.

PLoS Genet. 2009-8

引用本文的文献

[1]
Machine learning tools for deciphering the regulatory logic of enhancers in health and disease.

Front Genet. 2025-8-13

[2]
AutoMethyc: an automated methylation analysis for massively parallel sequencing data.

Brief Bioinform. 2025-7-2

[3]
Integrating Artificial Intelligence in Next-Generation Sequencing: Advances, Challenges, and Future Directions.

Curr Issues Mol Biol. 2025-6-19

[4]
Identifying ovarian cancer with machine learning DNA methylation pattern analysis.

Sci Rep. 2025-7-1

[5]
GraphAge: Unleashing the power of graph neural network to decode epigenetic aging.

PNAS Nexus. 2025-6-3

[6]
cfMethylPre: deep transfer learning enhances cancer detection based on circulating cell-free DNA methylation profiling.

Brief Bioinform. 2025-5-1

[7]
Artificial Intelligence in cancer epigenomics: a review on advances in pan-cancer detection and precision medicine.

Epigenetics Chromatin. 2025-6-14

[8]
Subtypes detection of papillary thyroid cancer from methylation assay via Deep Neural Network.

Comput Struct Biotechnol J. 2025-4-29

[9]
Epigenetic ageing clocks: statistical methods and emerging computational challenges.

Nat Rev Genet. 2025-5

[10]
Evaluation of agreement between common clustering strategies for DNA methylation-based subtyping of breast tumours.

Epigenomics. 2025-2

本文引用的文献

[1]
DNA methylation aging clocks: challenges and recommendations.

Genome Biol. 2019-11-25

[2]
DNA Methylation Markers for Pan-Cancer Prediction by Deep Learning.

Genes (Basel). 2019-10-4

[3]
Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1.

Genome Biol. 2019-8-14

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Bioinformatics. 2019-12-15

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Human epigenetic ageing is logarithmic with time across the entire lifespan.

Epigenetics. 2019-6-6

[6]
DeepSignal: detecting DNA methylation state from Nanopore sequencing reads using deep-learning.

Bioinformatics. 2019-11-1

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Blood DNA Methylation and Breast Cancer: A Prospective Case-Cohort Analysis in the Sister Study.

J Natl Cancer Inst. 2020-1-1

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Parameter tuning is a key part of dimensionality reduction via deep variational autoencoders for single cell RNA transcriptomics.

Pac Symp Biocomput. 2019

[9]
Methylation-Based Biological Age and Breast Cancer Risk.

J Natl Cancer Inst. 2019-10-1

[10]
A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.

PLoS Med. 2018-12-31

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