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RESEARCH Open Access On the design of clone-based haplotyping
BibTeX
@MISC{Lo_researchopen,
author = {Christine Lo and Rui Liu and Jehyuk Lee and Kimberly Robasky and Susan Byrne and Carolina Lucchesi and John Aach and George Church and Vineet Bafna and Kun Zhang},
title = {RESEARCH Open Access On the design of clone-based haplotyping},
year = {}
}
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Abstract
Background: Haplotypes are important for assessing genealogy and disease susceptibility of individual genomes, but are difficult to obtain with routine sequencing approaches. Experimental haplotype reconstruction based on assembling fragments of individual chromosomes is promising, but with variable yields due to incompletely understood parameter choices. Results: We parameterize the clone-based haplotyping problem in order to provide theoretical and empirical assessments of the impact of different parameters on haplotype assembly. We confirm the intuition that long clones help link together heterozygous variants and thus improve haplotype length. Furthermore, given the length of the clones, we address how to choose the other parameters, including number of pools, clone coverage and sequencing coverage, so as to maximize haplotype length. We model the problem theoretically and show empirically the benefits of using larger clones with moderate number of pools and sequencing coverage. In particular, using 140 kb BAC clones, we construct haplotypes for a personal genome and assemble haplotypes with N50 values greater than 2.6 Mb. These assembled haplotypes are longer and at least as accurate as haplotypes of existing clone-based strategies, whether in vivo or in vitro. Conclusions: Our results provide practical guidelines for the development and design of clone-based methods to
Keyphrases
clone-based haplotyping research open access haplotype length sequencing coverage long clone help moderate number heterozygous variant clone coverage assembled haplotype routine sequencing approach understood parameter choice clone-based method kb bac clone individual chromosome variable yield individual genome practical guideline clone-based haplotyping problem n50 value assemble haplotype experimental haplotype reconstruction clone-based strategy empirical assessment disease susceptibility personal genome different parameter haplotype assembly
