Imputing missing RNA-sequencing data from DNA methylation by using a transfer learning–based neural network

• Published in: Gigascience Vol. 9; no. 7
• Main Authors: Zhou, Xiang, Chai, Hua, Zhao, Huiying, Luo, Ching-Hsing, Yang, Yuedong
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.07.2020
• Subjects: Algorithms; Cancer; Cluster analysis; Clustering; Computational Biology - methods; CpG Islands; Datasets; Deoxyribonucleic acid; DNA; DNA Methylation; DNA sequencing; Epigenesis, Genetic; Epigenetics; Epigenomics - methods; Gene expression; Gene Expression Regulation; Gene sequencing; High-Throughput Nucleotide Sequencing; Humans; Information processing; Learning; Machine Learning; Medical prognosis; Neoplasms - diagnosis; Neoplasms - genetics; Neoplasms - mortality; Neural networks; Neural Networks, Computer; Phenotypes; Prognosis; Reproducibility of Results; Ribonucleic acid; RNA; RNA modification; Survival analysis; Transfer learning; DNA methylation; transfer learning; RNA-seq imputation; neural network
• ISSN: 2047-217X; 2047-217X
• DOI: 10.1093/gigascience/giaa076

Abstract Background Gene expression plays a key intermediate role in linking molecular features at the DNA level and phenotype. However, owing to various limitations in experiments, the RNA-seq data are missing in many samples while there exist high-quality of DNA methylation data. Because DNA methylation is an important epigenetic modification to regulate gene expression, it can be used to predict RNA-seq data. For this purpose, many methods have been developed. A common limitation of these methods is that they mainly focus on a single cancer dataset and do not fully utilize information from large pan-cancer datasets. Results Here, we have developed a novel method to impute missing gene expression data from DNA methylation data through a transfer learning–based neural network, namely, TDimpute. In the method, the pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized for training a general model, which was then fine-tuned on the specific cancer dataset. By testing on 16 cancer datasets, we found that our method significantly outperforms other state-of-the-art methods in imputation accuracy with a 7–11% improvement under different missing rates. The imputed gene expression was further proved to be useful for downstream analyses, including the identification of both methylation–driving and prognosis-related genes, clustering analysis, and survival analysis on the TCGA dataset. More importantly, our method was indicated to be useful for general purposes by an independent test on the Wilms tumor dataset from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project. Conclusions TDimpute is an effective method for RNA-seq imputation with limited training samples.