TY - JOUR T1 - Zero-shot imputations across species are enabled through joint modeling of human and mouse epigenomics JF - bioRxiv DO - 10.1101/801183 SP - 801183 AU - Jacob Schreiber AU - Deepthi Hegde AU - William Stafford Noble Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/01/31/801183.abstract N2 - Recent large-scale efforts to characterize the human epigenome have produced thousands of genome-wide experiments that quantify various forms of biological activity, such as histone modifications, protein binding, and chromatin accessibility. Although these experiments represent a small fraction of the possible experiments that could be performed, the human epigenome remains the most characterized epigenome of any species. We propose an extension to the imputation approach Avocado that enables the model to leverage the large number of human epigenomic data sets when making imputations in other species. We found that not only does this extension result in improved imputations of mouse epigenomics, but that the extended model is able to make accurate imputations for assays that have been performed in humans but not in mice. This ability to make “zero-shot” imputations greatly increases the utility of such imputation approaches, and enables comprehensive imputations to be made for species even when experimental data are sparse. Further, we found that our extension allows for an epigenomic similarity measure to be defined over pairs of regions across species based on Avocado’s learned representations. We show that this score can be used to identify regions with high sequence similarity whose function have diverged. ER -