Sequencing protocol and assembly methodology.

<p>Reads are obtained in a hierarchical sequencing protocol with high genome-clone coverage and low clone-read coverage. From the <i>k</i>-mer content of each clone we construct a clone graph whose edge weights reflect the likely clone proximities, and from this our clone ordering algorithm determines the clone contigs. Next, we find all putative read overlaps by only looking in nearby clones and perform error correction. In three stages of contig assembly we 1) create <i>read sets</i> via set operations that consist of reads from multiple overlapping clones within small clone subregions and assemble using <i>Euler</i>, 2) combine contigs resulting from the previous stage in clone-sized <i>contig sets</i> for assembly, and 3) use a scalable assembler to merge entire clone contigs.