VRP Assembler: haplotype-resolved de novo assembly of diploid and polyploid genomes using quantum computing

Abstract

Precision medicines emphasis on individual genetic variants highlights the importance of haplotype-resolved assembly, a computational challenge in bioinformatics given its combinatorial nature. While classical algorithms have made strides in addressing this issue, the potential of quantum computing remains largely untapped. Here, we present the VRP assembler: a novel approach that transforms this task into a vehicle routing problem, a combinatorial optimization problem solvable on a quantum computer. We demonstrate its potential and feasibility through a proof of concept on short synthetic diploid and triploid genomes using a D-Wave quantum annealer. To tackle larger-scale assembly problems, we integrate the VRP assembler with Googles OR-Tools, achieving a haplotype-resolved assembly across the human major histocompatibility complex (MHC) region. Our results show encouraging performance compared to hifiasm with the phasing accuracy first approaching the theoretical limit, underscoring the promising future of quantum computing in bioinformatics.