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Selecting Chromosomes for Polygenic Traits: Algorithms and Complexity

Authors: Or Zuk

Published in: LIPIcs, Volume 390, 26th International Conference on Algorithms for Bioinformatics (WABI 2026)


Abstract
We define and study the problem of genomic block selection for multiple complex traits. In this problem, one constructs a genome by selecting different genomic parts (e.g. chromosomes) from different source genomes. The constructed genome is associated with a vector of polygenic scores, obtained by summing the polygenic scores of the different genomic parts, and the goal is to minimize a given loss function of this vector. The problem is motivated by several emerging technologies: chromosome substitution lines in crop breeding, where chromosomal segments from wild relatives are combined to improve polygenic traits such as yield and stress tolerance; chromosome transfer between yeast strains for optimizing complex industrial phenotypes; and chromosomal transplantation technologies in mammalian cells. We suggest and study several natural loss functions relevant for both quantitative and threshold traits, and show that the problem is NP-complete even for a single trait and two copies, yet only weakly so, being pseudo-polynomially solvable for any fixed number of traits. We propose three algorithms with complementary roles: a Branch-and-Bound algorithm that returns the certified global optimum for any monotone loss, a fast Block-Coordinate-Descent (BCD) heuristic with random restarts that applies to any loss, and a semidefinite-programming (SDP) relaxation that provides a certified lower bound on the optimal loss for quadratic losses, and hence an optimality-gap bound when paired with the BCD solution - empirically tight in our experiments. Using the infinitesimal model for genetic architecture, we further derive, for linear losses, a closed-form approximation for the expected gain of block selection relative to random selection across multiple traits. On yeast-scale simulations BCD matches the certified Branch-and-Bound optimum on 100% of threshold-loss instances at 466× the speed, attains a certified optimality gap of at most ≈10% of the SDP lower bound for stabilizing-loss instances, and the realized gain roughly matches the analytic prediction.

Cite as

Or Zuk. Selecting Chromosomes for Polygenic Traits: Algorithms and Complexity. In 26th International Conference on Algorithms for Bioinformatics (WABI 2026). Leibniz International Proceedings in Informatics (LIPIcs), Volume 390, pp. 28:1-28:20, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2026)


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@InProceedings{zuk:LIPIcs.WABI.2026.28,
  author =	{Zuk, Or},
  title =	{{Selecting Chromosomes for Polygenic Traits: Algorithms and Complexity}},
  booktitle =	{26th International Conference on Algorithms for Bioinformatics (WABI 2026)},
  pages =	{28:1--28:20},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-446-8},
  ISSN =	{1868-8969},
  year =	{2026},
  volume =	{390},
  editor =	{El-Mabrouk, Nadia and Vandin, Fabio},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2026.28},
  URN =		{urn:nbn:de:0030-drops-275325},
  doi =		{10.4230/LIPIcs.WABI.2026.28},
  annote =	{Keywords: polygenic scores, combinatorial optimization, genomic block selection, NP-hardness, semidefinite programming, synthetic genomics}
}

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