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

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 pa...

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Bibliographic Details
Main Authors: Wang Xi, Michael A Beer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-12-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1006625
Description
Summary: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.
ISSN:1553-734X
1553-7358