Short read fragment assembly of bacterial genomes

Abstract

In the last year, high-throughput sequencing technologies have progressed from proof-of-concept to production quality. While these methods produce high-quality reads, they have yet to produce reads comparable in length to Sanger-based sequencing. Current fragment assembly algorithms have been implemented and optimized for mate-paired Sanger-based reads, and thus do not perform well on short reads produced by short read technologies. We present a new Eulerian assembler that generates nearly optimal short read assemblies of bacterial genomes and describe an approach to assemble reads in the case of the popular hybrid protocol when short and long Sanger-based reads are combined.

Figure 1.

Assembly of S. pneumoniae using 454 reads complemented with simulated Sanger reads (3000 ± 300 bp spacing). Uniformly distributed 800 base reads were generated for coverage varying from 1× to 5×, and then assembled using EULER-SR. We show the assembly using mate-pairs (solid), assembly using unpaired Sanger reads (broken), and the base assembly quality of 454 reads (dotted).

Figure 2.

A tandem repeat as a whirl consisting of two edges in the condensed de Bruijn graph, and its transformation into a tandem duplication with multiplicity 2. The bold edge is the repeat, and the broken edge represents the sequence between the consecutive copies of the repeat.