Genome assembly and comparison using de Bruijn graphs by Daniel Robert Zerbino. (thesis)
Abstract:
Recent advances in sequencing technology made it possible to generate vast amounts of sequence data. The fragments produced by these high-throughput methods are, however, far shorter than in traditional Sanger sequencing. Previously, micro-reads of less than 50 base pairs were considered useful only in the presence of an existing assembly. This thesis describes solutions for assembling short read sequencing data de novo, in the absence of a reference genome.
The algorithms developed here are based on the de Bruijn graph. This data structure is highly suitable for the assembly and comparison of genomes for the following reasons. It provides a flexible tool to handle the sequence variants commonly found in genome evolution such as duplications, inversions or transpositions. In addition, it can combine sequences of highly different lengths, from short reads to assembled genomes. Finally, it ensures an effective data compression of highly redundant datasets.
This thesis presents the development of a collection of methods, called Velvet, to convert a de Bruijn graph into a traditional assembly of contiguous sequences. The first step of the process, termed Tour Bus, removes sequencing errors and handles biological variations such as polymorphisms. In its second part, Velvet aims to resolve repeats based on the available information, from low coverage long reads (Rock Band) or paired shotgun reads (Pebble). These methods were tested on various simulations for precision and efficiency, then on control experimental datasets.
De Bruijn graphs can also be used to detect and analyse structural variants from unassembled data. The final chapter of this thesis presents the results of collaborative work on the analysis of several experimental unassembled datasets.
De Bruijn graphs are covered in pages 22-42 if you want to cut to the chase.
Obviously of interest to the bioinformatics community.
Where else would you use de Bruijn graph structures?