Computational Pan-Genomics: Status, Promises and Challenges

Abstract

Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic datasets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this paper, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies, and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains. * The Computational Pan-Genomics Consortium formed at a workshop held June 8-12, 2015, at the Lorentz Center in Leiden, the Netherlands, with the purpose of providing a cross-disciplinary overview of the emerging discipline of Computational Pan-Genomics. Members are listed at the end of this article.

Coordinates and Intervals in Graph-based Reference Genomes

“…Defining a coordinate system on such graph-based reference genomes has been discussed by Marschall et al [2]. They propose that nearby bases should have similar coordinates (spatiality), that coordinates should be concise and interpretable (readability), and that coordinates should increment along the genome (monotonicity).…”

Overlap graphs and de Bruijn graphs: data structures for de novogenome assembly in the big data era

“…The fastest algorithm to date was able to process seven whole mammalian genomes in under eight hours [82]. This makes feasible to attack another problem: pan‐genome assembly [83], that is the construction of the assembly graph of several individual genomes.…”

Snowball: strain aware gene assembly of metagenomes

“…In particular, low-abundance strains can interfere with sequencing errors in common error correction routines. To date, most assembly tools still aim to assemble consensus sequence, if closely related haplotypes are present (Marschall et al, 2016).…”