Dataset Information

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

ABSTRACT: For cancer diagnosis, many DNA methylation markers have been identified. However, few studies have tried to identify DNA methylation markers to diagnose diverse cancer types simultaneously, i.e., pan-cancers. In this study, we tried to identify DNA methylation markers to differentiate cancer samples from the respective normal samples in pan-cancers. We collected whole genome methylation data of 27 cancer types containing 10,140 cancer samples and 3386 normal samples, and divided all samples into five data sets, including one training data set, one validation data set and three test data sets. We applied machine learning to identify DNA methylation markers, and specifically, we constructed diagnostic prediction models by deep learning. We identified two categories of markers: 12 CpG markers and 13 promoter markers. Three of 12 CpG markers and four of 13 promoter markers locate at cancer-related genes. With the CpG markers, our model achieved an average sensitivity and specificity on test data sets as 92.8% and 90.1%, respectively. For promoter markers, the average sensitivity and specificity on test data sets were 89.8% and 81.1%, respectively. Furthermore, in cell-free DNA methylation data of 163 prostate cancer samples, the CpG markers achieved the sensitivity as 100%, and the promoter markers achieved 92%. For both marker types, the specificity of normal whole blood was 100%. To conclude, we identified methylation markers to diagnose pan-cancers, which might be applied to liquid biopsy of cancers.

SUBMITTER: Liu B

PROVIDER: S-EPMC6826785 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Liu Biao B Liu Yulu Y Pan Xingxin X Li Mengyao M Yang Shuang S Li Shuai Cheng SC

Genes 20191004 10

For cancer diagnosis, many DNA methylation markers have been identified. However, few studies have tried to identify DNA methylation markers to diagnose diverse cancer types simultaneously, i.e., pan-cancers. In this study, we tried to identify DNA methylation markers to differentiate cancer samples from the respective normal samples in pan-cancers. We collected whole genome methylation data of 27 cancer types containing 10,140 cancer samples and 3386 normal samples, and divided all samples into ...[more]

PMID: 31590287

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Project description:BackgroundDNA methylation is a key epigenetic regulator contributing to cancer development. To understand the role of DNA methylation in tumorigenesis, it is important to investigate and compare differential methylation (DM) patterns between normal and case samples across different cancer types. However, current pan-cancer analyses call DM separately for each cancer, which suffers from lower statistical power and fails to provide a comprehensive view for patterns across cancers.MethodsIn this work, we propose a rigorous statistical model, PanDM, to jointly characterize DM patterns across diverse cancer types. PanDM uses the hidden correlations in the combined dataset to improve statistical power through joint modeling. PanDM takes summary statistics from separate analyses as input and performs methylation site clustering, differential methylation detection, and pan-cancer pattern discovery. We demonstrate the favorable performance of PanDM using simulation data. We apply our model to 12 cancer methylome data collected from The Cancer Genome Atlas (TCGA) project. We further conduct ontology- and pathway-enrichment analyses to gain new biological insights into the pan-cancer DM patterns learned by PanDM.ResultsPanDM outperforms two types of separate analyses in the power of DM calling in the simulation study. Application of PanDM to TCGA data reveals 37 pan-cancer DM patterns in the 12 cancer methylomes, including both common and cancer-type-specific patterns. These 37 patterns are in turn used to group cancer types. Functional ontology and biological pathways enriched in the non-common patterns not only underpin the cancer-type-specific etiology and pathogenesis but also unveil the common environmental risk factors shared by multiple cancer types. Moreover, we also identify PanDM-specific DM CpG sites that the common strategy fails to detect.ConclusionsPanDM is a powerful tool that provides a systematic way to investigate aberrant methylation patterns across multiple cancer types. Results from real data analyses suggest a novel angle for us to understand the common and specific DM patterns in different cancers. Moreover, as PanDM works on the summary statistics for each cancer type, the same framework can in principle be applied to pan-cancer analyses of other functional genomic profiles. We implement PanDM as an R package, which is freely available at http://www.sta.cuhk.edu.hk/YWei/PanDM.html .

Project description:BackgroundRecent research recommends that epi-transcriptome regulation through post-transcriptional RNA modifications is essential for all sorts of RNA. Exact identification of RNA modification is vital for understanding their purposes and regulatory mechanisms. However, traditional experimental methods of identifying RNA modification sites are relatively complicated, time-consuming, and laborious. Machine learning approaches have been applied in the procedures of RNA sequence features extraction and classification in a computational way, which may supplement experimental approaches more efficiently. Recently, convolutional neural network (CNN) and long short-term memory (LSTM) have been demonstrated achievements in modification site prediction on account of their powerful functions in representation learning. However, CNN can learn the local response from the spatial data but cannot learn sequential correlations. And LSTM is specialized for sequential modeling and can access both the contextual representation but lacks spatial data extraction compared with CNN. There is strong motivation to construct a prediction framework using natural language processing (NLP), deep learning (DL) for these reasons.ResultsThis study presents an ensemble multiscale deep learning predictor (EMDLP) to identify RNA methylation sites in an NLP and DL way. It organically combines the dilated convolution and Bidirectional LSTM (BiLSTM), which helps to take better advantage of the local and global information for site prediction. The first step of EMDLP is to represent the RNA sequences in an NLP way. Thus, three encodings, e.g., RNA word embedding, One-hot encoding, and RGloVe, which is an improved learning method of word vector representation based on GloVe, are adopted to decipher sites from the viewpoints of the local and global information. Then, a dilated convolutional Bidirectional LSTM network (DCB) model is constructed with the dilated convolutional neural network (DCNN) followed by BiLSTM to extract potential contributing features for methylation site prediction. Finally, these three encoding methods are integrated by a soft vote to obtain better predictive performance. Experiment results on m1A and m6A reveal that the area under the receiver operating characteristic(AUROC) of EMDLP obtains respectively 95.56%, 85.24%, and outperforms the state-of-the-art models. To maximize user convenience, a user-friendly webserver for EMDLP was publicly available at http://www.labiip.net/EMDLP/index.php ( http://47.104.130.81/EMDLP/index.php ).ConclusionsWe developed a predictor for m1A and m6A methylation sites.

Dataset Information

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

Publications

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

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