Efficient Haplotype Inference with Pseudo-Boolean Optimization

Abstract. Haplotype inference from genotype data is a key computational problem in bioinformatics, since retrieving directly haplotype information from DNA samples is not feasible using existing technology. One of the methods for solving this problem uses the pure parsimony criterion, an approach known as Haplotype Inference by Pure Parsimony (HIPP). Initial work in this area was based on a number of different Integer Linear Programming (ILP) models and branch and bound algorithms. Recent work has shown that the utilization of a Boolean Satisfiability (SAT) formulation and state of the art SAT solvers represents the most efficient approach for solving the HIPP problem. Motivated by the promising results obtained using SAT techniques, this paper investigates the utilization of modern Pseudo-Boolean Optimization (PBO) algorithms for solving the HIPP problem. The paper starts by applying PBO to existing ILP models. The results are promising, and motivate the development of a new PBO model (RPoly) for the HIPP problem, which has a compact representation and eliminates key symmetries. Experimental results indicate that RPoly outperforms the SAT-based approach on most problem instances, being, in general, significantly more efficient

SPABBATS: A pathway-discovery method based on Boolean satisfiability that facilitates the characterization of suppressor mutants

BACKGROUND: Several computational methods exist to suggest rational genetic interventions that improve the productivity of industrial strains. Nonetheless, these methods are less effective to predict possible genetic responses of the strain after the intervention. This problem requires a better understanding of potential alternative metabolic and regulatory pathways able to counteract the targeted intervention. RESULTS: Here we present SPABBATS, an algorithm based on Boolean satisfiability (SAT) that computes alternative metabolic pathways between input and output species in a reconstructed network. The pathways can be constructed iteratively in order of increasing complexity. SPABBATS allows the accumulation of intermediates in the pathways, which permits discovering pathways missed by most traditional pathway analysis methods. In addition, we provide a proof of concept experiment for the validity of the algorithm. We deleted the genes for the glutamate dehydrogenases of the Gram-positive bacterium Bacillus subtilis and isolated suppressor mutant strains able to grow on glutamate as single carbon source. Our SAT approach proposed candidate alternative pathways which were decisive to pinpoint the exact mutation of the suppressor strain. CONCLUSIONS: SPABBATS is the first application of SAT techniques to metabolic problems. It is particularly useful for the characterization of metabolic suppressor mutants and can be used in a synthetic biology setting to design new pathways with specific input-output requirements

Quantum Algorithm for Variant Maximum Satisfiability

In this paper, we proposed a novel quantum algorithm for the maximum satisfiability problem. Satisfiability (SAT) is to find the set of assignment values of input variables for the given Boolean function that evaluates this function as TRUE or prove that such satisfying values do not exist. For a POS SAT problem, we proposed a novel quantum algorithm for the maximum satisfiability (MAX-SAT), which returns the maximum number of OR terms that are satisfied for the SAT-unsatisfiable function, providing us with information on how far the given Boolean function is from the SAT satisfaction. We used Grover’s algorithm with a new block called quantum counter in the oracle circuit. The proposed circuit can be adapted for various forms of satisfiability expressions and several satisfiability-like problems. Using the quantum counter and mirrors for SAT terms reduces the need for ancilla qubits and realizes a large Toffoli gate that is then not needed. Our circuit reduces the number of ancilla qubits for the terms T of the Boolean function from T of ancilla qubits to ≈⌈log2⁡T⌉+1. We analyzed and compared the quantum cost of the traditional oracle design with our design which gives a low quantum cost

Haplotype inference from unphased SNP data in heterozygous polyploids based on SAT

<p>Abstract</p> <p>Background</p> <p>Haplotype inference based on unphased SNP markers is an important task in population genetics. Although there are different approaches to the inference of haplotypes in diploid species, the existing software is not suitable for inferring haplotypes from unphased SNP data in polyploid species, such as the cultivated potato (<it>Solanum tuberosum</it>). Potato species are tetraploid and highly heterozygous.</p> <p>Results</p> <p>Here we present the software SATlotyper which is able to handle polyploid and polyallelic data. SATlo-typer uses the Boolean satisfiability problem to formulate Haplotype Inference by Pure Parsimony. The software excludes existing haplotype inferences, thus allowing for calculation of alternative inferences. As it is not known which of the multiple haplotype inferences are best supported by the given unphased data set, we use a bootstrapping procedure that allows for scoring of alternative inferences. Finally, by means of the bootstrapping scores, it is possible to optimise the phased genotypes belonging to a given haplotype inference. The program is evaluated with simulated and experimental SNP data generated for heterozygous tetraploid populations of potato. We show that, instead of taking the first haplotype inference reported by the program, we can significantly improve the quality of the final result by applying additional methods that include scoring of the alternative haplotype inferences and genotype optimisation. For a sub-population of nineteen individuals, the predicted results computed by SATlotyper were directly compared with results obtained by experimental haplotype inference via sequencing of cloned amplicons. Prediction and experiment gave similar results regarding the inferred haplotypes and phased genotypes.</p> <p>Conclusion</p> <p>Our results suggest that Haplotype Inference by Pure Parsimony can be solved efficiently by the SAT approach, even for data sets of unphased SNP from heterozygous polyploids. SATlotyper is freeware and is distributed as a Java JAR file. The software can be downloaded from the webpage of the GABI Primary Database at <url>http://www.gabipd.org/projects/satlotyper/</url>. The application of SATlotyper will provide haplotype information, which can be used in haplotype association mapping studies of polyploid plants.</p

Quantum Search Algorithms for Constraint Satisfaction and Optimization Problems Using Grover\u27s Search and Quantum Walk Algorithms with Advanced Oracle Design

The field of quantum computing has emerged as a powerful tool for solving and optimizing combinatorial optimization problems. To solve many real-world problems with many variables and possible solutions for constraint satisfaction and optimization problems, the required number of qubits of scalable hardware for quantum computing is the bottleneck in the current generation of quantum computers. In this dissertation, we will demonstrate advanced, scalable building blocks for the quantum search algorithms that have been implemented in Grover\u27s search algorithm and the quantum walk algorithm. The scalable building blocks are used to reduce the required number of qubits in the design. The proposed architecture effectively scales and optimizes the number of qubits needed to solve large problems with a limited number of qubits. Thus, scaling and optimizing the number of qubits that can be accommodated in quantum algorithm design directly reflect on performance. Also, accuracy is a key performance metric related to how accurately one can measure quantum states. The search space of quantum search algorithms is traditionally created by using the Hadamard operator to create superposition. However, creating superpositions for problems that do not need all superposition states decreases the accuracy of the measured states. We present an efficient quantum circuit design that the user has control over to create the subspace superposition states for the search space as needed. Using only the subspace states as superposition states of the search space will increase the rate of correct solutions. In this dissertation, we will present the implementation of practical problems for Grover\u27s search algorithm and quantum walk algorithm in logic design, logic puzzles, and machine learning problems such as SAT, MAX-SAT, XOR-SAT, and like SAT problems in EDA, and mining frequent patterns for association rule mining