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Minimum Segmentation for Pan-genomic Founder Reconstruction in Linear Time

Authors Tuukka Norri , Bastien Cazaux , Dmitry Kosolobov , Veli Mäkinen

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ACM Subject Classification
  • Theory of computation → Design and analysis of algorithms
  • Applied computing → Bioinformatics
Keywords
  • Pan-genome indexing
  • founder reconstruction
  • dynamic programming
  • positional Burrows-Wheeler transform
  • range minimum query

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Abstract

Given a threshold L and a set R = {R_1, ..., R_m} of m strings (haplotype sequences), each having length n, the minimum segmentation problem for founder reconstruction is to partition [1,n] into set P of disjoint segments such that each segment [a,b] in P has length at least L and the number d(a,b)=|{R_i[a,b] : 1 <= i <= m}| of distinct substrings at segment [a,b] is minimized over [a,b] in P. The distinct substrings in the segments represent founder blocks that can be concatenated to form max{d(a,b) : [a,b] in P} founder sequences representing the original R such that crossovers happen only at segment boundaries. We give an optimal O(mn) time algorithm to solve the problem, improving over earlier O(mn^2). This improvement enables to exploit the algorithm on a pan-genomic setting of input strings being aligned haplotype sequences of complete human chromosomes, with a goal of finding a representative set of references that can be indexed for read alignment and variant calling. We implemented the new algorithm and give some experimental evidence on the practicality of the approach on this pan-genomic setting.

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Tuukka Norri, Bastien Cazaux, Dmitry Kosolobov, and Veli Mäkinen. Minimum Segmentation for Pan-genomic Founder Reconstruction in Linear Time. In 18th International Workshop on Algorithms in Bioinformatics (WABI 2018). Leibniz International Proceedings in Informatics (LIPIcs), Volume 113, pp. 15:1-15:15, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2018) https://doi.org/10.4230/LIPIcs.WABI.2018.15

Author Details

Tuukka Norri
  • Department of Computer Science, University of Helsinki, Helsinki, Finland
Bastien Cazaux
  • Department of Computer Science, University of Helsinki, Helsinki, Finland
Dmitry Kosolobov
  • Department of Computer Science, University of Helsinki, Helsinki, Finland
Veli Mäkinen
  • Department of Computer Science, University of Helsinki, Helsinki, Finland

Funding

This work is partially supported by the Academy of Finland (grant 309048).

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