Refinement of protein structure models with multi-objective genetic algorithms

Here I investigate the protein structure refinement problem for homology-based protein structure models. The refinement problem has been identified as a major bottleneck in the structure prediction process and inhibits the goal of producing high-resolution experimental quality structures for target protein sequences. This thesis is composed of three investigations into aspects of template-based modelling and refinement. In the primary investigation, empirical evidence is provided to support the hypothesis that using multiple template-based structures to model a target sequence can improve the quality of the prediction over that obtained solely by using the single best prediction. A multi-objective genetic algorithm is used to optimize protein structure models by using the structural information from a set of predictions, guided by various objective functions. The effect of multi-objective optimization on model quality is examined. A benchmark of energy functions and model quality assessment methods is performed in the context of automated homology modelling to assess the ability of these methods at discriminating nearer-native structures from a set of predictions. These model quality assessment methods were unable to significantly improve the ranking of threading- based prediction methods though some model quality assessment methods improved model selection for methods which use sequence information alone. The results suggest that structural informational can provide valuable information for distinguishing better models where only sequence information has been used for modelling. The suitability of these energy functions for high-resolution refinement is discussed. Finally, a stochastic optimization algorithm is developed for refining homology-based protein structure models using evolutionary algorithms. This approach uses multiple structural model inputs, conformational sampling operators, and objective functions for guiding a search through conformational space. Single- and multi-objective genetic variants are applied to homology model predictions for 35 target proteins. The refinement results are discussed and the performance of both algorithmic variants compared and contrasted

Learning Deep Similarity Metric for 3D MR-TRUS Registration

Purpose: The fusion of transrectal ultrasound (TRUS) and magnetic resonance (MR) images for guiding targeted prostate biopsy has significantly improved the biopsy yield of aggressive cancers. A key component of MR-TRUS fusion is image registration. However, it is very challenging to obtain a robust automatic MR-TRUS registration due to the large appearance difference between the two imaging modalities. The work presented in this paper aims to tackle this problem by addressing two challenges: (i) the definition of a suitable similarity metric and (ii) the determination of a suitable optimization strategy. Methods: This work proposes the use of a deep convolutional neural network to learn a similarity metric for MR-TRUS registration. We also use a composite optimization strategy that explores the solution space in order to search for a suitable initialization for the second-order optimization of the learned metric. Further, a multi-pass approach is used in order to smooth the metric for optimization. Results: The learned similarity metric outperforms the classical mutual information and also the state-of-the-art MIND feature based methods. The results indicate that the overall registration framework has a large capture range. The proposed deep similarity metric based approach obtained a mean TRE of 3.86mm (with an initial TRE of 16mm) for this challenging problem. Conclusion: A similarity metric that is learned using a deep neural network can be used to assess the quality of any given image registration and can be used in conjunction with the aforementioned optimization framework to perform automatic registration that is robust to poor initialization.Comment: To appear on IJCAR

Human Arm simulation for interactive constrained environment design

During the conceptual and prototype design stage of an industrial product, it is crucial to take assembly/disassembly and maintenance operations in advance. A well-designed system should enable relatively easy access of operating manipulators in the constrained environment and reduce musculoskeletal disorder risks for those manual handling operations. Trajectory planning comes up as an important issue for those assembly and maintenance operations under a constrained environment, since it determines the accessibility and the other ergonomics issues, such as muscle effort and its related fatigue. In this paper, a customer-oriented interactive approach is proposed to partially solve ergonomic related issues encountered during the design stage under a constrained system for the operator's convenience. Based on a single objective optimization method, trajectory planning for different operators could be generated automatically. Meanwhile, a motion capture based method assists the operator to guide the trajectory planning interactively when either a local minimum is encountered within the single objective optimization or the operator prefers guiding the virtual human manually. Besides that, a physical engine is integrated into this approach to provide physically realistic simulation in real time manner, so that collision free path and related dynamic information could be computed to determine further muscle fatigue and accessibility of a product designComment: International Journal on Interactive Design and Manufacturing (IJIDeM) (2012) 1-12. arXiv admin note: substantial text overlap with arXiv:1012.432

Spatial optimization for land use allocation: accounting for sustainability concerns

Land-use allocation has long been an important area of research in regional science. Land-use patterns are fundamental to the functions of the biosphere, creating interactions that have substantial impacts on the environment. The spatial arrangement of land uses therefore has implications for activity and travel within a region. Balancing development, economic growth, social interaction, and the protection of the natural environment is at the heart of long-term sustainability. Since land-use patterns are spatially explicit in nature, planning and management necessarily must integrate geographical information system and spatial optimization in meaningful ways if efficiency goals and objectives are to be achieved. This article reviews spatial optimization approaches that have been relied upon to support land-use planning. Characteristics of sustainable land use, particularly compactness, contiguity, and compatibility, are discussed and how spatial optimization techniques have addressed these characteristics are detailed. In particular, objectives and constraints in spatial optimization approaches are examined

Enhanced genetic algorithm-based fuzzy multiobjective strategy to multiproduct batch plant design

This paper addresses the problem of the optimal design of batch plants with imprecise demands in product amounts. The design of such plants necessary involves how equipment may be utilized, which means that plant scheduling and production must constitute a basic part of the design problem. Rather than resorting to a traditional probabilistic approach for modeling the imprecision on product demands, this work proposes an alternative treatment by using fuzzy concepts. The design problem is tackled by introducing a new approach based on a multiobjective genetic algorithm, combined wit the fuzzy set theory for computing the objectives as fuzzy quantities. The problem takes into account simultaneous maximization of the fuzzy net present value and of two other performance criteria, i.e. the production delay/advance and a flexibility index. The delay/advance objective is computed by comparing the fuzzy production time for the products to a given fuzzy time horizon, and the flexibility index represents the additional fuzzy production that the plant would be able to produce. The multiobjective optimization provides the Pareto's front which is a set of scenarios that are helpful for guiding the decision's maker in its final choices. About the solution procedure, a genetic algorithm was implemented since it is particularly well-suited to take into account the arithmetic of fuzzy numbers. Furthermore because a genetic algorithm is working on populations of potential solutions, this type of procedure is well adapted for multiobjective optimization

Adaptive Weighted Expected Improvement With Rewards Approach in Kriging Assisted Electromagnetic Design

The paper explores kriging surrogate modelling combined with expected improvement approach for the design of electromagnetic devices. A novel algorithm based on the concept of rewards is proposed, tested and demonstrated in the context of TEAM Workshop Problem 22. Balancing exploration and exploitation is emphasized and robustness of the design considered