QuImputer: an LD-informed QUBO/Ising formulation of genotype imputation with quantum-hardware execution
Abstract
Genotype imputation offers a biological application for optimization methods that may eventually run on larger quantum computers. We developed QuImputer to encode allele-frequency priors and signed linkage disequilibrium (LD) in a reduced Ising/QUBO objective, with only missing genotypes represented as optimization variables. The same objective can be passed to exhaustive classical search, quantum approximate optimization algorithm simulation, or quantum hardware. We evaluated the formulation on 100 rice accessions across 12 chromosomes, estimating LD and allele frequency from the same post-masking observed matrix supplied to Beagle 5.4. Evaluation was restricted to known truth at sites with exact dosage coding and an alternate allele that was not the major allele, with MAF below 0.50, yielding 1.88 billion scored genotypes. Beagle achieved higher rare-ALT sensitivity (2.52% versus 0.54%), F1 (0.047 versus 0.011), Matthews correlation coefficient (0.088 versus 0.044), and pooled hard-call dosage R-squared (0.231 versus 0.014). QuImputer produced fewer false ALT calls, with Type I error of 0.038% versus 0.223%. Analyses of a chromosome-1 subset showed limited local LD support for many masked rare-ALT carriers. In five small IBM Fez validation problems, the selected minimum-energy outputs matched unique all-reference exact optima; the pooled frequency of those optima was 1.21-2.63%. Further IBM Fez executions covered eleven sparse instances with 12-97 variables and a separate…
Read the paper
Related studies
- Chaos and quantum thermalization
- The Dalton quantum chemistry program system
- Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study
- Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes
- Stable adiabatic quantum batteries
- A novel self-lipid antigen targets human T cells against CD1c(+) leukemias
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.