Linear Time Probabilistic Algorithms for the Singular Haplotype Reconstruction Problem from SNP Fragments

Chen, Zhixiang; Fu, Bin; Schweller, Robert T.; Yang, Boting; Zhao, Zhiyu; Zhu, Binhai

doi:10.1089/cmb.2008.0003

Cited by 33 publications

(10 citation statements)

References 16 publications

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“…Two more algorithms are mentioned in (23), a randomized one called SHRThree (31), and SpeedHap (32) which tries to build first a core solution with variants and fragments with full agreement and evidence of presence of the two alleles for each variant, and then includes the remaining fragments and variants by relaxing constraints. Among all these algorithms, HapCUT was the only one for which there was an implementation available to be applied to real data and to perform independent validation.…”

Section: Methodsmentioning

confidence: 99%

Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of Single Individual Haplotyping techniques

Duitama

McEwen

Huebsch

et al. 2011

Nucleic Acids Research

113

152

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Determining the underlying haplotypes of individual human genomes is an essential, but currently difficult, step toward a complete understanding of genome function. Fosmid pool-based next-generation sequencing allows genome-wide generation of 40-kb haploid DNA segments, which can be phased into contiguous molecular haplotypes computationally by Single Individual Haplotyping (SIH). Many SIH algorithms have been proposed, but the accuracy of such methods has been difficult to assess due to the lack of real benchmark data. To address this problem, we generated whole genome fosmid sequence data from a HapMap trio child, NA12878, for which reliable haplotypes have already been produced. We assembled haplotypes using eight algorithms for SIH and carried out direct comparisons of their accuracy, completeness and efficiency. Our comparisons indicate that fosmid-based haplotyping can deliver highly accurate results even at low coverage and that our SIH algorithm, ReFHap, is able to efficiently produce high-quality haplotypes. We expanded the haplotypes for NA12878 by combining the current haplotypes with our fosmid-based haplotypes, producing near-to-complete new gold-standard haplotypes containing almost 98% of heterozygous SNPs. This improvement includes notable fractions of disease-related and GWA SNPs. Integrated with other molecular biological data sets, this phase information will advance the emerging field of diploid genomics.

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Section: Methodsmentioning

confidence: 99%

Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of Single Individual Haplotyping techniques

Duitama

McEwen

Huebsch

et al. 2011

Nucleic Acids Research

113

152

View full text Add to dashboard Cite

show abstract

“…In [23], Geraci compared the reconstruction rates of seven state-of-the-art algorithms on the same benchmark datasets. These seven algorithms are SpeedHap [24], Fast hare [25], 2d-mec [26], HapCUT [21], MLF [27], SHR-three [28] and DGS, the greedy heuristic proposed in [20]. For a full review of these seven algorithms, the reader is referred to [23].…”

Section: Resultsmentioning

confidence: 99%

A highly accurate heuristic algorithm for the haplotype assembly problem

2013

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BackgroundSingle nucleotide polymorphisms (SNPs) are the most common form of genetic variation in human DNA. The sequence of SNPs in each of the two copies of a given chromosome in a diploid organism is referred to as a haplotype. Haplotype information has many applications such as gene disease diagnoses, drug design, etc. The haplotype assembly problem is defined as follows: Given a set of fragments sequenced from the two copies of a chromosome of a single individual, and their locations in the chromosome, which can be pre-determined by aligning the fragments to a reference DNA sequence, the goal here is to reconstruct two haplotypes (h1, h2) from the input fragments. Existing algorithms do not work well when the error rate of fragments is high. Here we design an algorithm that can give accurate solutions, even if the error rate of fragments is high.ResultsWe first give a dynamic programming algorithm that can give exact solutions to the haplotype assembly problem. The time complexity of the algorithm is O(n × 2t × t), where n is the number of SNPs, and t is the maximum coverage of a SNP site. The algorithm is slow when t is large. To solve the problem when t is large, we further propose a heuristic algorithm on the basis of the dynamic programming algorithm. Experiments show that our heuristic algorithm can give very accurate solutions.ConclusionsWe have tested our algorithm on a set of benchmark datasets. Experiments show that our algorithm can give very accurate solutions. It outperforms most of the existing programs when the error rate of the input fragments is high.

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“…In Chen et al (2008), the authors proposed a probabilistic framework to approach the SIH problem. According to the proposed model, the authors designed a novel randomized algorithm [i.e.…”

Section: Algorithmsmentioning

confidence: 99%

A comparison of several algorithms for the single individual SNP haplotyping reconstruction problem

Geraci

2010

Bioinformatics

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Motivation: Single nucleotide polymorphisms are the most common form of variation in human DNA, and are involved in many research fields, from molecular biology to medical therapy. The technological opportunity to deal with long DNA sequences using shotgun sequencing has raised the problem of fragment recombination. In this regard, Single Individual Haplotyping (SIH) problem has received considerable attention over the past few years.Results: In this article, we survey seven recent approaches to the SIH problem and evaluate them extensively using real human haplotype data from the HapMap project. We also implemented a data generator tailored to the current shotgun sequencing technology that uses haplotypes from the HapMap project.Availability: The data we used to compare the algorithms are available on demand, since we think they represent an important benchmark that can be used to easily compare novel algorithmic ideas with the state of the art. Moreover, we had to re-implement six of the algorithms surveyed because the original code was not available to us. Five of these algorithms and the data generator used in this article endowed with a Web interface are available at http://bioalgo.iit.cnr.it/rehapContact: filippo.geraci@iit.cnr.it

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Linear Time Probabilistic Algorithms for the Singular Haplotype Reconstruction Problem from SNP Fragments

Cited by 33 publications

References 16 publications

Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of Single Individual Haplotyping techniques

Fosmid-based whole genome haplotyping of a HapMap trio child: evaluation of Single Individual Haplotyping techniques

A highly accurate heuristic algorithm for the haplotype assembly problem

A comparison of several algorithms for the single individual SNP haplotyping reconstruction problem

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