Asymmetric predictive relationships across histone modifications

Decoding the epigenomic landscapes in diverse tissues and cell types is fundamental to understanding molecular mechanisms underlying many essential cellular processes and human diseases. Recent advances in artificial intelligence provide new methods and strategies for imputing unknown epigenomes based on existing data, yet how to reveal the predictive relationships among epigenetic marks remains largely unexplored. Here we present a machine learning approach for epigenomic imputation and interpretation. Through dissection of the spatial contributions from six histone marks, we reveal the prevalent and asymmetric cross-prediction relationships among these marks. Meanwhile, our approach achieved high predictive performance on held-out prospective epigenomes and outperformed the state-of-the-art. To facilitate future research, we further applied this approach to impute a total of 527 and 2,455 unavailable genome-wide histone modification signal tracks for the ENCODE3 and Roadmap datasets, respectively.