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Tractatus: An Exact and Subquadratic Algorithm for Inferring Identical-by-Descent Multi-shared Haplotype Tracts

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Research in Computational Molecular Biology (RECOMB 2014)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 8394))

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Abstract

In this work we present graph theoretic algorithms for the identification of all identical-by-descent (IBD) multi-shared haplotype tracts for an m ×n haplotype matrix. We introduce Tractatus, an exact algorithm for computing all IBD haplotype tracts in time linear in the size of the input, O(mn). Tractatus resolves a long standing open problem, breaking optimally the (worst-case) quadratic time barrier of O(m 2 n) of previous methods often cited as a bottleneck in haplotype analysis of genome-wide association study-sized data. This advance in algorithm efficiency makes an impact in a number of areas of population genomics rooted in the seminal Li-Stephens framework for modeling multi-loci linkage disequilibrium (LD) patterns with applications to the estimation of recombination rates, imputation, haplotype-based LD mapping, and haplotype phasing. We extend the Tractatus algorithm to include computation of haplotype tracts with allele mismatches and shared homozygous haplotypes in a set of genotypes. Lastly, we present a comparison of algorithmic runtime, power to infer IBD tracts, and false positive rates for simulated data and computations of homozygous haplotypes in genome-wide association study data of autism. The Tractatus algorithm is available for download at http://www.brown.edu/Research/Istrail_Lab/ .

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Aguiar, D., Morrow, E., Istrail, S. (2014). Tractatus: An Exact and Subquadratic Algorithm for Inferring Identical-by-Descent Multi-shared Haplotype Tracts. In: Sharan, R. (eds) Research in Computational Molecular Biology. RECOMB 2014. Lecture Notes in Computer Science(), vol 8394. Springer, Cham. https://doi.org/10.1007/978-3-319-05269-4_1

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  • DOI: https://doi.org/10.1007/978-3-319-05269-4_1

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-05268-7

  • Online ISBN: 978-3-319-05269-4

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