# Optimal Assembly for High Throughput Shotgun Sequencing

How to judge how good a genome assembly algorithm is ? Mathematically inclined readers may take a look at an interesting paper submitted to arxiv.org.

DNA sequencing is the basic workhorse of modern day biology and medicine. Shotgun sequencing is the dominant technique used: many randomly located short fragments called reads are extracted from the DNA sequence, and these reads are assembled to reconstruct the original sequence. During the last two decades, many assembly algorithms have been proposed, but comparing and evaluating them is difficult. To clarify this, we ask: Given N reads of length L sampled from an arbitrary DNA sequence, is it possible to achieve some target probability 1? of successful reconstruction? We show that the answer depends on the repeat statistics of the DNA sequence to be assembled, and we compute these statistics for a number of reference genomes. We construct lower bounds showing that reconstruction is impossible for certain choices of N and L, and complement this by analytically deriving the performance of several algorithms, both in terms of repeat statistics. In seeking an algorithm that matches the lower bounds on real DNA data, we are able to methodically progress towards an optimal assembly algorithm. The goal of this work is to advocate a new systematic approach to the design of assembly algorithms with optimality or near-optimality guarantee.