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.