An Eulerian path approach to DNA fragment assembly

For the last 20 years, fragment assembly in DNA sequencing followed the “overlap–layout–consensus” paradigm that is used in all currently available assembly tools. Although this approach proved useful in assembling clones, it faces difficulties in genomic shotgun assembly. We abandon the classical “overlap–layout–consensus” approach in favor of a new euler algorithm that, for the first time, resolves the 20-year-old “repeat problem” in fragment assembly. Our main result is the reduction of the fragment assembly to a variation of the classical Eulerian path problem that allows one to generate accurate solutions of large-scale sequencing problems. euler , in contrast to the celera assembler, does not mask such repeats but uses them instead as a powerful fragment assembly tool.