Local epigenomic state cannot discriminate interacting and non-interacting enhancer-promoter pairs with high accuracy

PLoS Comput Biol. 2018 Dec 18;14(12):e1006625. doi: 10.1371/journal.pcbi.1006625. eCollection 2018 Dec.

Abstract

We report an experimental design issue in recent machine learning formulations of the enhancer-promoter interaction problem arising from the fact that many enhancer-promoter pairs share features. Cross-fold validation schemes which do not correctly separate these feature sharing enhancer-promoter pairs into one test set report high accuracy, which is actually arising from high training set accuracy and a failure to properly evaluate generalization performance. Cross-fold validation schemes which properly segregate pairs with shared features show markedly reduced ability to predict enhancer-promoter interactions from epigenomic state. Parameter scans with multiple models indicate that local epigenomic features of individual pairs of enhancers and promoters cannot distinguish those pairs that interact from those which do with high accuracy, suggesting that additional information is required to predict enhancer-promoter interactions.

Publication types

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

MeSH terms

  • Cell Line
  • Computational Biology
  • Enhancer Elements, Genetic*
  • Epigenesis, Genetic*
  • Humans
  • K562 Cells
  • Machine Learning
  • Models, Genetic*
  • Promoter Regions, Genetic*
  • Support Vector Machine