期刊
BMC BIOINFORMATICS
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12859-020-3443-8
关键词
Deep learning; DNA methylation; High performance computing; Workflow automation; Unsupervised; Supervised; Transfer learning; Embedding
类别
资金
- NIH [R01CA216265, R01DE022772, P20GM104416]
- Dartmouth College Neukom Institute for Computational Science CompX award
- Burroughs Wellcome Fund Big Data in the Life Sciences training grant at Dartmouth
- [T32LM012204]
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.
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