An overview on nucleic-acid G-quadruplex prediction: from rule-based methods to deep neural networks

Karin Elimelech-Zohar, Yaron Orenstein

Research output: Contribution to journalReview articlepeer-review


Nucleic-acid G-quadruplexes (G4s) play vital roles in many cellular processes. Due to their importance, researchers have developed experimental assays to measure nucleic-acid G4s in high throughput. The generated high-throughput datasets gave rise to unique opportunities to develop machine-learning-based methods, and in particular deep neural networks, to predict G4s in any given nucleic-acid sequence and any species. In this paper, we review the success stories of deep-neural-network applications for G4 prediction. We first cover the experimental technologies that generated the most comprehensive nucleic-acid G4 high-throughput datasets in recent years. We then review classic rule-based methods for G4 prediction. We proceed by reviewing the major machine-learning and deep-neural-network applications to nucleic-acid G4 datasets and report a novel comparison between them. Next, we present the interpretability techniques used on the trained neural networks to learn key molecular principles underlying nucleic-acid G4 folding. As a new result, we calculate the overlap between measured DNA and RNA G4s and compare the performance of DNA- and RNA-G4 predictors on RNA- and DNA-G4 datasets, respectively, to demonstrate the potential of transfer learning from DNA G4s to RNA G4s. Last, we conclude with open questions in the field of nucleic-acid G4 prediction and computational modeling.

Original languageEnglish
Article numberbbad252
JournalBriefings in Bioinformatics
Issue number4
StatePublished - 20 Jul 2023


  • G-quadruplex
  • deep learning
  • deep neural network
  • interpretability
  • transfer learning

All Science Journal Classification (ASJC) codes

  • Information Systems
  • Molecular Biology


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