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Application of Multi-Objective Optimization to Pooled Experiments of Next Generation Sequencing for Detection of Rare Mutations

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  • Julius Žilinskas
  • Algirdas Lančinskas
  • Mario Rosario Guarracino

Abstract

In this paper we propose some mathematical models to plan a Next Generation Sequencing experiment to detect rare mutations in pools of patients. A mathematical optimization problem is formulated for optimal pooling, with respect to minimization of the experiment cost. Then, two different strategies to replicate patients in pools are proposed, which have the advantage to decrease the overall costs. Finally, a multi-objective optimization formulation is proposed, where the trade-off between the probability to detect a mutation and overall costs is taken into account. The proposed solutions are devised in pursuance of the following advantages: (i) the solution guarantees mutations are detectable in the experimental setting, and (ii) the cost of the NGS experiment and its biological validation using Sanger sequencing is minimized. Simulations show replicating pools can decrease overall experimental cost, thus making pooling an interesting option.

Suggested Citation

  • Julius Žilinskas & Algirdas Lančinskas & Mario Rosario Guarracino, 2014. "Application of Multi-Objective Optimization to Pooled Experiments of Next Generation Sequencing for Detection of Rare Mutations," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-9, September.
  • Handle: RePEc:plo:pone00:0104992
    DOI: 10.1371/journal.pone.0104992
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    References listed on IDEAS

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    1. Altannar Chinchuluun & Panos Pardalos, 2007. "A survey of recent developments in multiobjective optimization," Annals of Operations Research, Springer, vol. 154(1), pages 29-50, October.
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