Reducing Genome Assembly Complexity with Optical Maps Final Report

The goal of genome assembly is to reconstruct contiguous portions of a genome (known as contigs) given short reads of DNA sequence obtained in a sequencing experiment. De Bruijn graphs are constructed by finding overlaps of length k − 2 between all substrings of length k − 1 from reads of at least k bases, resulting in a graph where the correct reconstruction of the genome is given by one of the many possible Eulerian tours. The assembly problem is complicated by genomic repeats, which allow for exponentially many possible Eulerian tours, thereby increasing the de Bruijn graph complexity. Optical maps provide an ordered listing of restriction fragment sizes for a given enzyme across an entire chromosome, and therefore give long range information that can be useful in resolving genomic repeats. The algorithms presented here align contigs to an optical map and then use the constraints of these alignments to find paths through the assembly graph that resolve genomic repeats, thereby reducing the assembly graph complexity. The goal of this project is to implement the Contig-Optical Map Alignment Tool and the Assembly Graph Simplification Tool and to use these tools to simplify the idealized de Bruijn graphs on a database of 351 prokaryotic genomes.