Enhanced Integrated Gradients: improving interpretability of deep learning models using splicing codes as a case study

Genome Biol. 2020 Jun 19;21(1):149. doi: 10.1186/s13059-020-02055-7.

Abstract

Despite the success and fast adaptation of deep learning models in biomedical domains, their lack of interpretability remains an issue. Here, we introduce Enhanced Integrated Gradients (EIG), a method to identify significant features associated with a specific prediction task. Using RNA splicing prediction as well as digit classification as case studies, we demonstrate that EIG improves upon the original Integrated Gradients method and produces sets of informative features. We then apply EIG to identify A1CF as a key regulator of liver-specific alternative splicing, supporting this finding with subsequent analysis of relevant A1CF functional (RNA-seq) and binding data (PAR-CLIP).

Keywords: A1CF; Deep learning; Interpretation; Liver-specific splicing; Splicing code.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Computational Biology / methods*
  • Deep Learning*
  • Liver / metabolism
  • Mice, Knockout
  • RNA Splicing*