Completing the ENCODE3 compendium yields accurate imputations across a variety of assays and human biosamples

MotivationRecent efforts to describe the human epigenome have yielded thousands of uniformly processed epigenomic and transcriptomic data sets. These data sets characterize a rich variety of biological activity in hundreds of human cell lines and tissues ("biosamples"). Understanding these data sets, and specifically how they differ across biosamples, can help explain many cellular mechanisms, particularly those driving development and disease. However, due primarily to cost, the total number of assays that can be performed is limited. Previously described imputation approaches, such as Avocado, have sought to overcome this limitation by predicting genome-wide epigenomics experiments using learned associations among available epigenomic data sets. However, these previous imputations have focused primarily on measurements of histone modification and chromatin accessibility, despite other biological activity being crucially important. ResultsWe applied Avocado to a data set of 3,814 tracks of data derived from the ENCODE compendium, spanning 400 human biosamples and 84 assays. The resulting imputations cover measurements of chromatin accessibility, histone modification, transcription, and protein binding. We demonstrate the quality of these imputations by comprehensively evaluating the models predictions and by showing significant improvements in protein binding performance compared to the top models in an ENCODE-DREAM challenge. Additionally, we show that the Avocado model allows for efficient addition of new assays and biosamples to a pre-trained model, achieving high accuracy at predicting protein binding, even with only a single track of training data. AvailabilityTutorials and source code are available under an Apache 2.0 license at https://github.com/jmschrei/avocado. Contactwilliam-noble@uw.edu or jmschr@cs.washington.edu