The fragment assembly problem is that of reconstructing a DNA sequence from a collection of randomly sampled fragments. Traditionally the objective of this problem has been to produce the shortest string that contains all the fragments as substrings, but in the case of repetitive target sequences this objective produces answers that are overcompressed. In this paper, the problem is reformulated as one of finding a maximum-likelihood reconstruction with respect to the 2-sided Kolmogorov-Smirnov statistic, and it is argued that this is a better formulation of the problem. Next the fragment assembly problem is recast in graph-theoretic terms as one of finding a non-cyclic subgraph with certain properties and the objectives of being shortest or maximally-likely are also recast in this framework. Finally, a series of graph reduction transformations are given that dramatically reduce the size of the graph to be explored in practical instances of the problem. This reduction is ...

this article describes three current approaches for completing the sequencing.

ABSTRACT We introduce and develop new techniques to quantify DNA patchiness, and to quantify characteristics of its mosaic structure. These techniques, which involve calculating two functions, a(f) and f3(f), measure correlations at length scale e and detect distinct characteristic patch sizes embedded in scale-invariant patch size distributions. Using these new methods, we address a number of issues relating to the mosaic structure of genomic DNA. We find several distinct characteristic patch sizes in certain genomic sequences, and compare, contrast, and quantify the correlation properties of different sequences, including a number of yeast, human, and prokaryotic sequences. We exclude the possibility that the correlation properties and the known mosaic structure of DNA can be explained either by simple Markov processes or by tandem repeats of dinucleotides. We find that the distinct patch sizes in all 16 yeast chromosomes are similar. Furthermore, we test the hypothesis that, for yeast, patchiness is caused by the alternation of coding and noncoding regions, and the hypothesis that in human sequences patchiness is related to repetitive sequences. We find that, by themselves, neither the alternation of coding and noncoding regions, nor repetitive sequences, can fully explain the long-range correlation properties of DNA.

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