Abstract

Comparative epigenomics, which subjects both epigenome and genome to interspecies comparison, has become a powerful approach to reveal regulatory features of the genome. Thus elucidated regulatory features surpass the information derived from comparison of genomic sequences alone. Here, we present EpiAlignment, a web-based tool to align genomic regions with both DNA sequence and epigenomic data. EpiAlignment takes DNA sequence and epigenomic profiles derived by ChIP-seq from two species as input data, and outputs the best semi-global alignments. These alignments are based on EpiAlignment scores, computed by a dynamic programming algorithm that accounts for both sequence alignment and epigenome similarity. For timely response, the EpiAlignment web server automatically initiates up to 140 computing threads depending on the size of user input data. For users’ convenience, we have pre-compiled the comparable human and mouse epigenome datasets in matched cell types and tissues from the Roadmap Epigenomics and ENCODE consortia. Users can either upload their own data or select pre-compiled datasets as inputs for EpiAlignment analyses. Results are presented in graphical and tabular formats where the entries can be interactively expanded to visualize additional features of these aligned regions. EpiAlignment is available at https://epialign.ucsd.edu/.

Highlights

  • Epigenomic modifications contribute to the implementation of genomic functions in defining cell identity, coordinating organismal development [1,2], and regulating personal cognition and behavior [3,4]

  • Given the advances in analytical methods and the explosive growth of epigenomic data, a computational tool for the integrative comparison of the genome and the epigenome is in demand

  • The aligned regions can be further visualized in the UCSC genome browser [26] and the Genomic Interaction Visualization Engine (GIVE) [19] by following links provided in the result tables

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Summary

INTRODUCTION

Epigenomic modifications contribute to the implementation of genomic functions in defining cell identity, coordinating organismal development [1,2], and regulating personal cognition and behavior [3,4]. A set of recent efforts have established the proof of principle that comparative analyses of interspecies epigenomes can lead to functional annotation of non-coding regulatory genomic sequences [5,6]. These regulatory sequences could not be discovered by sequence comparison alone, due to obscure sequence conservation that is likely a result of intricate interplays of negative and positive selections on nested sequence segments [7,8]. The most recent efforts have expanded interspecies comparisons to incorporate the 3D organization of the genome [20,21,22] These efforts highlight how comparative epigenomics, an emerging field, leverages evolutionary patterns of epigenomes to functionally annotate genomes. The aligned regions can be further visualized in the UCSC genome browser [26] and the Genomic Interaction Visualization Engine (GIVE) [19] by following links provided in the result tables

METHODS AND IMPLEMENTATION
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