Two-locus model is a typical significant disease model to be identified in genome-wide association study (GWAS). Due to intensive computational burden and diversity of disease models, existing methods have drawbacks on low detection power, high computation cost, and preference for some types of disease models. In this study, two scoring functions (Bayesian network based K2-score and Gini-score) are used for characterizing two SNP locus as a candidate model, the two criteria are adopted simultaneously for improving identification power and tackling the preference problem to disease models. Harmony search algorithm (HSA) is improved for quickly finding the most likely candidate models among all two-locus models, in which a local search algorithm with two-dimensional tabu table is presented to avoid repeatedly evaluating some disease models that have strong marginal effect. Finally G-test statistic is used to further test the candidate models. We investigate our method named FHSA-SED on 82 simulated datasets and a real AMD dataset, and compare it with two typical methods (MACOED and CSE) which have been developed recently based on swarm intelligent search algorithm. The results of simulation experiments indicate that our method outperforms the two compared algorithms in terms of detection power, computation time, evaluation times, sensitivity (TPR), specificity (SPC), positive predictive value (PPV) and accuracy (ACC). Our method has identified two SNPs (rs3775652 and rs10511467) that may be also associated with disease in AMD dataset.

Harmony search (HS) algorithm is an emerging population-based metaheuristic algorithm, which is inspired by the music improvisation process. The HS method has been developed rapidly and applied widely during the past decade. In this paper, an improved global harmony search algorithm, named harmony search based on teaching-learning (HSTL), is presented for high dimension complex optimization problems. In HSTL algorithm, four strategies (harmony memory consideration, teaching-learning strategy, local pitch adjusting, and random mutation) are employed to maintain the proper balance between convergence and population diversity, and dynamic strategy is adopted to change the parameters. The proposed HSTL algorithm is investigated and compared with three other state-of-the-art HS optimization algorithms. Furthermore, to demonstrate the robustness and convergence, the success rate and convergence analysis is also studied. The experimental results of 31 complex benchmark functions demonstrate that the HSTL method has strong convergence and robustness and has better balance capacity of space exploration and local exploitation on high dimension complex optimization problems.

Motivation: Recently, multiobjective swarm intelligence optimization (SIO) algorithms have attracted considerable attention as disease model-free methods for detecting high-order single nucleotide polymorphism (SNP) interactions. However, a strict Pareto optimal set may filter out some of the SNP combinations associated with disease status. Furthermore, the lack of heuristic factors for finding SNP interactions and the preference for discrimination approaches to disease models are considerable challenges for SIO. : In this study, we propose a multipopulation harmony search (HS) algorithm dedicated to the detection of high-order SNP interactions (MP-HS-DHSI). This method consists of three stages. In the first stage, HS with multipopulation (multiharmony memories) is used to discover a set of candidate high-order SNP combinations having an association with disease status. In HS, multiple criteria [Bayesian network-based K2-score, Jensen–Shannon divergence, likelihood ratio and normalized distance with joint entropy (ND-JE)] are adopted by four harmony memories to improve the ability to discriminate diverse disease models. A novel evaluation criterion named ND-JE is proposed to guide HS to explore clues for high-order SNP interactions. In the second and third stages, the G-test statistical method and multifactor dimensionality reduction are employed to verify the authenticity of the candidate solutions, respectively.Results: We compared MP-HS-DHSI with four state-of-the-art SIO algorithms for detecting high-order SNP interactions for 20 simulation disease models and a real dataset of age-related macular degeneration. The experimental results revealed that our proposed method can accelerate the search speed efficiently and enhance the discrimination ability of diverse epistasis models.Availability and implementation: https://github.com/shouhengtuo/MP-HS-DHSI.Supplementary information: Supplementary data are available at Bioinformatics online.

Genome-wide association study is especially challenging in detecting high-order disease-causing models due to model diversity, possible low or even no marginal effect of the model, and extraordinary search and computations. In this paper, we propose a niche harmony search algorithm where joint entropy is utilized as a heuristic factor to guide the search for low or no marginal effect model, and two computationally lightweight scores are selected to evaluate and adapt to diverse of disease models. In order to obtain all possible suspected pathogenic models, niche technique merges with HS, which serves as a taboo region to avoid HS trapping into local search. From the resultant set of candidate SNP-combinations, we use G-test statistic for testing true positives. Experiments were performed on twenty typical simulation datasets in which 12 models are with marginal effect and eight ones are with no marginal effect. Our results indicate that the proposed algorithm has very high detection power for searching suspected disease models in the first stage and it is superior to some typical existing approaches in both detection power and CPU runtime for all these datasets. Application to age-related macular degeneration (AMD) demonstrates our method is promising in detecting high-order disease-causing models.

Harmony Search (HS) and Teaching-Learning-Based Optimization (TLBO) as new swarm intelligent optimization algorithms have received much attention in recent years. Both of them have shown outstanding performance for solving NP-Hard optimization problems. However, they also suffer dramatic performance degradation for some complex high-dimensional optimization problems. Through a lot of experiments, we find that the HS and TLBO have strong complementarity each other. The HS has strong global exploration power but low convergence speed. Reversely, the TLBO has much fast convergence speed but it is easily trapped into local search. In this work, we propose a hybrid search algorithm named HSTLBO that merges the two algorithms together for synergistically solving complex optimization problems using a self-adaptive selection strategy. In the HSTLBO, both HS and TLBO are modified with the aim of balancing the global exploration and exploitation abilities, where the HS aims mainly to explore the unknown regions and the TLBO aims to rapidly exploit high-precision solutions in the known regions. Our experimental results demonstrate better performance and faster speed than five state-of-the-art HS variants and show better exploration power than five good TLBO variants with similar run time, which illustrates that our method is promising in solving complex high-dimensional optimization problems. The experiment on portfolio optimization problems also demonstrate that the HSTLBO is effective in solving complex read-world application.