Abstract
The single nucleotide polymorphism (SNP) is the most widely studied type of genetic variation. A haplotype is defined as the sequence of alleles at SNP sites on each haploid chromosome. Haplotype information is essential in unravelling the genome-phenotype association. Haplotype assembly is a well-known approach for reconstructing haplotypes, exploiting reads generated by DNA sequencing devices. The Minimum Error Correction (MEC) metric is often used for reconstruction of haplotypes from reads. However, problems with the MEC metric have been reported. Here, we investigate the MEC approach to demonstrate that it may result in incorrectly reconstructed haplotypes for devices that produce error-prone long reads. Specifically, we evaluate this approach for devices developed by Illumina, Pacific BioSciences and Oxford Nanopore Technologies. We show that imprecise haplotypes may be reconstructed with a lower MEC than that of the exact haplotype. The performance of MEC is explored for different coverage levels and error rates of data. Our simulation results reveal that in order to avoid incorrect MEC-based haplotypes, a coverage of 25 is needed for reads generated by Pacific BioSciences RS systems.
Highlights
Among the various types of genetic variations, single nucleotide polymorphisms (SNPs) are the most widely studied among others in genome wide association studies (GWAS)
We investigated the reliability of the Minimum Error Correction (MEC) approach for haplotype assembly
We demonstrate that in some practical circumstances, an imprecise haplotype may be reconstructed with a lower MEC than that of the exact haplotype
Summary
Among the various types of genetic variations, single nucleotide polymorphisms (SNPs) are the most widely studied among others in genome wide association studies (GWAS). The genome of diploids like humans consists of two homologous pairs: the paternal and maternal chromosomes. A haplotype, the sequence of alleles at SNP sites on each homologous chromosome, can be measured through direct experiments or can be reconstructed by computational approaches [1, 2]. Due to the high cost of experimental methods, the computational techniques have attracted more attention. These techniques can be categorized as phasing or assembly approaches. Phasing makes use of the genotypes of multiple individuals to infer the haplotype. In the haplotype assembly approach, sets of reads generated by DNA sequencing devices are exploited for haplotype reconstruction. While haplotype assembly can be performed for a single individual, phasing cannot. Phasing is difficult in the presence of low-frequency and de novo variants
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