Coordinates and intervals in graph-based reference genomes

Abstract

Background: It has been proposed that future reference genomes should be graph structures in order to better represent the sequence diversity present in a species. However, there is currently no standard method to represent genomic intervals, such as the positions of genes or transcription factor binding sites, on graph-based reference genomes. Results: We formalize offset-based coordinate systems on graph-based reference genomes and introduce methods for representing intervals on these reference structures. We show the advantage of our methods by representing genes on a graph-based representation of the newest assembly of the human genome (GRCh38) and its alternative loci for regions that are highly variable. Conclusion: More complex reference genomes, containing alternative loci, require methods to represent genomic data on these structures. Our proposed notation for genomic intervals makes it possible to fully utilize the alternative loci of the GRCh38 assembly and potential future graph-based reference genomes. We have made a Python package for representing such intervals on offset-based coordinate systems, available at https://github.com/uio-cels/offsetbasedgraph. An interactive web-tool using this Python package to visualize genes on a graph created from GRCh38 is available at https://github.com/uio-cels/genomicgraphcoords.