Nonvariational quantum optimisation approaches to pangenome-guided sequence assembly
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arXiv
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| Format: | Preprint |
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2026
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| _version_ | 1866918432598917120 |
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| author | Cudby, Josh Strelchuk, Sergii |
| author_facet | Cudby, Josh Strelchuk, Sergii |
| contents | Assembling genomes from short-read sequencing data remains difficult in repetitive regions, where reference bias and combinatorial complexity limit existing methods. Pangenome-guided sequence assembly (PGSA) mitigates reference bias by reconstructing an individual genome as a walk through a population-level graph. The associated problem, identifying a walk whose node visits match read-derived copy numbers, is NP-hard and already challenges classical solvers at a moderate scale. We develop near-term quantum optimisation approaches for this computational bottleneck. We consider two problem encodings: an established quadratic unconstrained binary optimisation and a new higher-order binary optimisation (HUBO) formulation. The latter reduces the number of variables from $O(N^2)$ to $O(N\log N)$ and places moderate-sized instances within the qubit budget of current devices. We solve both using the Iterative-QAOA framework, which combines a fixed linear-ramp QAOA schedule with iterative warm-start bias updates, avoiding the overhead of full variational parameter optimisation. A custom circuit compilation strategy reduces hardware gate overhead by up to 67\% compared with standard tools. In noiseless simulations of QUBO problems, Iterative-QAOA reliably identifies optimal assemblies from as few as $10^{-17}\%$ of all candidate solutions, and \textit{IBM} quantum hardware closely reproduces relevant results with sufficient sampling via CVaR-style post-selection. For HUBO, the variable reduction comes at the cost of deeper compiled circuits and greater noise sensitivity: an expected qubit--depth trade-off. Our findings establish pangenome assembly as a concrete, biologically motivated problem class at the scale where quantum optimisation may first provide practical value. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2604_06106 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Nonvariational quantum optimisation approaches to pangenome-guided sequence assembly Cudby, Josh Strelchuk, Sergii Quantum Physics Assembling genomes from short-read sequencing data remains difficult in repetitive regions, where reference bias and combinatorial complexity limit existing methods. Pangenome-guided sequence assembly (PGSA) mitigates reference bias by reconstructing an individual genome as a walk through a population-level graph. The associated problem, identifying a walk whose node visits match read-derived copy numbers, is NP-hard and already challenges classical solvers at a moderate scale. We develop near-term quantum optimisation approaches for this computational bottleneck. We consider two problem encodings: an established quadratic unconstrained binary optimisation and a new higher-order binary optimisation (HUBO) formulation. The latter reduces the number of variables from $O(N^2)$ to $O(N\log N)$ and places moderate-sized instances within the qubit budget of current devices. We solve both using the Iterative-QAOA framework, which combines a fixed linear-ramp QAOA schedule with iterative warm-start bias updates, avoiding the overhead of full variational parameter optimisation. A custom circuit compilation strategy reduces hardware gate overhead by up to 67\% compared with standard tools. In noiseless simulations of QUBO problems, Iterative-QAOA reliably identifies optimal assemblies from as few as $10^{-17}\%$ of all candidate solutions, and \textit{IBM} quantum hardware closely reproduces relevant results with sufficient sampling via CVaR-style post-selection. For HUBO, the variable reduction comes at the cost of deeper compiled circuits and greater noise sensitivity: an expected qubit--depth trade-off. Our findings establish pangenome assembly as a concrete, biologically motivated problem class at the scale where quantum optimisation may first provide practical value. |
| title | Nonvariational quantum optimisation approaches to pangenome-guided sequence assembly |
| topic | Quantum Physics |
| url | https://arxiv.org/abs/2604.06106 |