4.7 Article

DeepTorrent: a deep learning-based approach for predicting DNA N4-methylcytosine sites

Journal

BRIEFINGS IN BIOINFORMATICS
Volume 22, Issue 3, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bib/bbaa124

Keywords

DNA N4-methylcytosine sites; bioinformatics; sequence analysis; machine learning; deep learning

Funding

  1. National Health and Medical Research Council of Australia (NHMRC) [1092262]
  2. Australian Research Council (ARC) [LP110200333, DP120104460]
  3. National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01 AI111965]
  4. Major Inter-Disciplinary Research (IDR) project - Monash University
  5. Collaborative Research Program of Institute for Chemical Research, Kyoto University [2019-32]

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A deep learning approach named DeepTorrent is proposed for improved prediction of 4mC sites from DNA sequences, utilizing multi-layer convolutional neural networks with an inception module integrated with bidirectional long short-term memory to learn higher-order feature representations. Dimension reduction and concatenated feature maps from filters of different sizes are applied for prediction.
DNA N4-methylcytosine (4mC) is an important epigenetic modification that plays a vital role in regulating DNA replication and expression. However, it is challenging to detect 4mC sites through experimental methods, which are time-consuming and costly. Thus, computational tools that can identify 4mC sites would be very useful for understanding the mechanism of this important type of DNA modification. Several machine learning-based 4mC predictors have been proposed in the past 3 years, although their performance is unsatisfactory. Deep learning is a promising technique for the development of more accurate 4mC site predictions. In this work, we propose a deep learning-based approach, called DeepTorrent, for improved prediction of 4mC sites from DNA sequences. It combines four different feature encoding schemes to encode raw DNA sequences and employs multi-layer convolutional neural networks with an inception module integrated with bidirectional long short-term memory to effectively learn the higher-order feature representations. Dimension reduction and concatenated feature maps from the filters of different sizes are then applied to the inception module. In addition, an attention mechanism and transfer learning techniques are also employed to train the robust predictor. Extensive benchmarking experiments demonstrate that DeepTorrent significantly improves the performance of 4mC site prediction compared with several state-of-the-art methods.

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