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THEORY AND ALGORITHMS FOR THE HAPLOTYPE ASSEMBLY PROBLEM
, 2010
"... Genome sequencing studies to date have generally sought to assemble consensus genomes by merging sequence contributions from multiple homologous copies of each chromosome. With growing interest in genetic variations, however, there is a need for methods to separate these distinct contributions and ..."
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Genome sequencing studies to date have generally sought to assemble consensus genomes by merging sequence contributions from multiple homologous copies of each chromosome. With growing interest in genetic variations, however, there is a need for methods to separate these distinct contributions and assess how individual homologous chromosome copies differ from one another. An approach to this problem was developed using small sequence fragments derived from shotgun sequencing studies to determine the patterns of variations that co-occur on individual chromosomes. This has become known as the “haplotype assembly ” problem. This review paper surveys results on the theory and algorithms for haplotype assembly. It first describes common abstractions of the problem. It then discusses some notable intractibility results for different problem variants. It next examines a variety of combinatorial, statistical, and heuristic methods for assembling fragment data sets in practice. The review concludes with a discussion of recent directions in diploid genome sequencing and their implications for haplotype assembly in the future.
ReHap: AN INTEGRATED SYSTEM FOR THE HAPLOTYPE ASSEMBLY PROBLEM FROM SHOTGUN SEQUENCING DATA Preparation of Camera-Ready Contributions to INSTICC Proceedings
"... Single nucleotide polymorphism (SNP) is the most common form of DNA variation. The set of SNPs present in a chromosome (called the haplotype) is of interest in a wide area of applications in molecular biology and biomedicine. Personalized haplotyping of (portions of/all) the chromosomes of individua ..."
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Single nucleotide polymorphism (SNP) is the most common form of DNA variation. The set of SNPs present in a chromosome (called the haplotype) is of interest in a wide area of applications in molecular biology and biomedicine. Personalized haplotyping of (portions of/all) the chromosomes of individuals is one of the most promising basic ingredients leading to effective personalized medicine (including diagnosis, and eventually therapy). Personalized haplotyping is getting now technically and economically feasible via steady progress in shotguns sequencing technologies (see e.g. the 1000 genomes project- A deep catalogue of human genetic variations). One key algorithmic problem in this process is to solve the haplotype assembly problem, (also known as the single individual haplotyping problem), which is the problem of reconstructing the two haplotype strings (paternal and maternal) using the large collection of short fragments produced by the PCR-based shotgun technology. Although many algorithms for this problem have been proposed in the literature there has been little progress on the task of comparing them on a common basis and on providing support for selecting the best algorithm for the type of fragments generated by a specific experiment. In this paper we present Re-Hap, an easy-to-use AJAX based web tool that provides a complete experimental environment for comparing five different assembly algorithms under a variety of parameters setting, taking as input user generated data and/or providing several fragment-generation simulation tools. This is the first published report of a comparison among five different haplotype assembly algorithms on a common data and algorithmic framework. This system can be used by researchers freely at the