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Hybrid De Novo Genome Assembly for the Generation of Complete Genomes of Urinary Bacteria using Short- and Long-read Sequencing Technologies
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On the complexity of Minimum Path Cover with Subpath Constraints for multi-assembly.

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    This study addresses complex multi-assembly problems in genomics by extending the Minimum Path Cover (MPC) problem. We show long-read constraints are efficiently solvable, while paired-end read constraints are NP-hard but fixed-parameter tractable.

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    Area of Science:

    • Computational Biology
    • Bioinformatics
    • Graph Theory

    Background:

    • Next-Generation Sequencing (NGS) technologies enable multi-assembly analyses of complex biological data like RNA-Seq and viral quasi-species.
    • The Minimum Path Cover (MPC) problem on directed acyclic graphs is a foundational model for many multi-assembly methods.
    • Classical MPC is polynomial-time solvable due to graph acyclicity.

    Purpose of the Study:

    • To investigate two generalizations of the MPC problem incorporating constraints from long reads (subpaths) and paired-end reads (pairs of subpaths).
    • To develop efficient algorithms for these generalized MPC problems in the context of multi-assembly challenges.

    Main Methods:

    • For long reads, a reduction to the classical MPC problem is employed, including a weighted variant solved via min-cost circulation.
    • For paired-end reads, the problem is shown to be NP-hard, but fixed-parameter tractable (FPT) with respect to the number of constraints.
    • Improvements to the time complexity of the classical minimum weight MPC problem are also presented.

    Main Results:

    • The generalized MPC problem with subpath constraints (long reads) is solved in polynomial time.
    • The generalized MPC problem with pairs of subpath constraints (paired-end reads) is NP-hard but FPT.
    • The study reveals a computational dichotomy between handling long reads and paired-end reads in multi-assembly.

    Conclusions:

    • The developed methods provide efficient solutions for specific multi-assembly problems arising from NGS data.
    • The findings offer insights into the computational complexity of integrating different read types in genome assembly.
    • This work contributes to advancing algorithms for reconstructing complex biological sequences.