ReHap: AN INTEGRATED SYSTEM FOR THE HAPLOTYPE ASSEMBLY PROBLEM FROM SHOTGUN SEQUENCING DATA

摘要

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 haplo-type 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 url: http://bioalgo.iit.cnr.it/rehap/.