Issue No. 02 - April-June (2008 vol. 5)
Emerging microarray technologies allow affordable typing of very long genome sequences. A key challenge in analyzing of such huge amount of data is scalable and accurate computational inferring of haplotypes (i.e., splitting of each genotype into a pair of corresponding haplotypes). In this paper, we first phase genotypes consisting only of two SNPs using genotypes frequencies adjusted to the random mating model and then extend phasing of two-SNP genotypes to phasing of complete genotypes using maximum spanning trees. Runtime of the proposed 2SNP algorithm is $O(nm (n + \log m)$, where n and m are the numbers of genotypes and SNPs, respectively, and it can handle genotypes spanning entire chromosomes in a matter of hours.On datasets across 23 chromosomal regions from HapMap, 2SNP is several orders of magnitude faster than GERBIL and PHASE while matching them in quality measured by the number of correctly phased genotypes, single-site and switching errors. For example the 2SNP software phases entire chromosome ($10^5$ SNPs from HapMap) for 30 individuals in 2 hours with average switching error 7.7%.We have also enhanced 2SNP algorithm to phase family trio data and compared it with four other well-known phasing methods on simulated data from . 2SNP is much faster than all of them while loosing in quality only to PHASE. 2SNP software is publicly available at http://alla.cs.gsu.edu/~software/2SNP.
SNP, genotype, haplotype, phasing, algorithm
D. Brinza and A. Zelikovsky, "2SNP: Scalable Phasing Method for Trios and Unrelated Individuals," in IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 5, no. , pp. 313-318, 2007.