Deciphering RNA splicing logic with interpretable machine learning

Susan E. Liao, Mukund Sudarshan, Oded Regev

Research output: Contribution to journalArticlepeer-review


Machine learning methods, particularly neural networks trained on large datasets, are transforming how scientists approach scientific discovery and experimental design. However, current state-of-the-art neural networks are limited by their uninterpretability: Despite their excellent accuracy, they cannot describe how they arrived at their predictions. Here, using an “interpretable-by-design” approach, we present a neural network model that provides insights into RNA splicing, a fundamental process in the transfer of genomic information into functional biochemical products. Although we designed our model to emphasize interpretability, its predictive accuracy is on par with state-of-the-art models. To demonstrate the model’s interpretability, we introduce a visualization that, for any given exon, allows us to trace and quantify the entire decision process from input sequence to output splicing prediction. Importantly, the model revealed uncharacterized components of the splicing logic, which we experimentally validated. This study highlights how interpretable machine learning can advance scientific discovery.

Original languageEnglish (US)
Article numbere2221165120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - 2023


  • RNA splicing
  • artificial intelligence
  • interpretable machine learning

ASJC Scopus subject areas

  • General


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