How to Reconstruct a Genome

Abstract

Since its early formulations (e.g., [1]), the genome assembly problem has attracted lots of interest from algorithm theoretic as well as from algorithm engineering point of view. In this problem, which is an inversion problem by nature, one is asked to reconstruct the entire DNA sequence from the short, randomly picked sequence fragments that a DNA sequencing instrument is able to read [2]. With the invent of current high-throughput sequencers producing such fragment reads in massive amounts, there is in molecular biology research a pronounced call for an accurate and fast reconstruction procedure.

It is customary to structure a reconstruction procedure into the following major steps: (1) Error correction of the fragments; (2) Finding pairwise overlaps between the fragments and representing the overlaps as a graph; (3) Constructing approximate superstrings, called contigs, for the fragments; (4) Constructing a linear order, called a scaffold, of the contigs. All steps are algorithmically challenging. Noisy data and intricate repetition structure of the target genome cause added difficulties. The talk attempts to give an overall picture of the genome assembly process and its algorithmic aspects emphasizing some recent developments in error correction [3], contig assembly, and scaffolding [4]. We also try to convey experiences from a major undertaking of de novo sequencing of a higher organism, Glanville fritillary butterfly Melitea cinxia. (A collaboration with I. Hanski, www.helsinki.fi/science/metapop/index.htm ).