Minimum Segmentation for Pan-genomic Founder Reconstruction in Linear Time

Abstract

Given a threshold $L$ and a set $\mathcal{R} = \{R_1, \ldots, R_m\}$ of $m$ haplotype sequences, each having length $n$, the minimum segmentation problem for founder reconstruction is to partition the sequences into disjoint segments $\mathcal{R}[i_1{+}1,i_2], \mathcal{R}[i_2{+}1, i_3], \ldots, \mathcal{R}[i_{r-1}{+}1, i_r]$, where $0 = i_1 < \cdots < i_r = n$ and $\mathcal{R}[i_{j-1}{+}1, i_j]$ is the set $\{R_1[i_{j-1}{+}1, i_j], \ldots, R_m[i_{j-1}{+}1, i_j]\}$, such that the length of each segment, $i_j - i_{j-1}$, is at least $L$ and $K = \max_j\{ |\mathcal{R}[i_{j-1}{+}1, i_j]| \}$ is minimized. The distinct substrings in the segments $\mathcal{R}[i_{j-1}{+}1, i_j]$ represent founder blocks that can be concatenated to form $K$ founder sequences representing the original $\mathcal{R}$ 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 haplotypes being complete human chromosomes, with a goal of finding a representative set of references that can be indexed for read alignment and variant calling.