Madhu Chetty

Weaving computational grids: how analogous are they with electrical grids?

Can computational grids make as great an impact in the 21st century as electrical grids did in the 20th? A comparison of the two technologies could provide clues about how to make computational grids pervasive, dependable, and convenient. In this article, we describe how computational grids developed, their layered structure, and their emerging operational model, which we envisage as providing seamless, utility-like access to computational resources. We also attempt to show the similarities and dissimilarities between this system, still in its infancy, and the mature electrical power grid. By identifying quantities and parameters that are analogous between the two grids, we hope that we can bring to light areas in computational grid development that need more focus.

Twin Removal in Genetic Algorithms for Protein Structure Prediction Using Low-Resolution Model

This paper presents the impact of twins and the measures for their removal from the population of genetic algorithm (GA) when applied to effective conformational searching. It is conclusively shown that a twin removal strategy for a GA provides considerably enhanced performance when investigating solutions to complex ab initio protein structure prediction (PSP) problems in low-resolution model. Without twin removal, GA crossover and mutation operations can become ineffectual as generations lose their ability to produce significant differences, which can lead to the solution stalling. The paper relaxes the definition of chromosomal twins in the removal strategy to not only encompass identical, but also highly correlated chromosomes within the GA population, with empirical results consistently exhibiting significant improvements solving PSP problems.

GlobalMIT: learning globally optimal dynamic bayesian network with the mutual information test criterion

MOTIVATION Dynamic Bayesian networks (DBN) are widely applied in modeling various biological networks including the gene regulatory network (GRN). Due to the NP-hard nature of learning static Bayesian network structure, most methods for learning DBN also employ either local search such as hill climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing. RESULTS This article presents GlobalMIT, a toolbox for learning the globally optimal DBN structure from gene expression data. We propose using a recently introduced information theoretic-based scoring metric named mutual information test (MIT). With MIT, the task of learning the globally optimal DBN is efficiently achieved in polynomial time. AVAILABILITY The toolbox, implemented in Matlab and C++, is available at http://code.google.com/p/globalmit. CONTACT vinh.nguyen@monash.edu; madhu.chetty@monash.edu SUPPLEMENTARY INFORMATION Supplementary data is available at Bioinformatics online.

Protein folding prediction in 3D FCC HP lattice model using genetic algorithm

In most of the successful real protein structure prediction (PSP) problem, lattice models have been essentially utilized to have the folding backbone sampling at the top of the hierarchical approach. A three dimensional face-centred-cube (FCC), with the provision for providing the most compact core, can map closest to the folded protein in reality. Hence, our successful hybrid genetic algorithms (HGA) proposed earlier for a square and cube lattice model is being extended in this paper for a 3D FCC model. Furthermore, twins (conformations having similarity with each other), in GA population have also been considered for removal from the search space for improving the effectiveness of GA The HGA combined with the twin removal (TR) strategy showed best performance when compared with the simple GA (SGA), SGA with TR, and HGA only versions. Experiments were carried out on the publicly available benchmark HP sequences and results are expressed based on the fitness of the corresponding applied lattice model, which will help any future novel approach to be compared.

Extended HP Model for Protein Structure Prediction

This paper describes a detailed investigation of a lattice-based HP (hydrophobic-hydrophilic) model for ab initio protein structure prediction (PSP). The outcome of the simplified HP lattice model has high degeneracy, which could mislead the prediction. The HPNX model was proposed to address the degeneracy problem as well as to avoid the conformational deformity with the hydrophilic (P) residues. We have experimentally shown that it is necessary to further improve the existing HPNX model. We have found and solved the critical error of another existing YhHX model. By extracting the significant features from the YhHX for the HPNX model, we have proposed a novel hHPNX model. Hybrid Genetic Algorithm (HGA) has been used to compare the predictability of these models and hHPNX outperformed other models. We preferred 3D face-centered-cube (FCC) lattice configuration to have closest resemblance to the real folded 3D protein.

A Guided Genetic Algorithm for Protein Folding Prediction Using 3D Hydrophobic-Hydrophilic Model

In this paper, a Guided Genetic Algorithm (GGA) has been presented for protein folding prediction (PFP) using 3D Hydrophobic-Hydrophilic (HP) model. Effective strategies have been formulated utilizing the core formation of the globular protein, which provides the guideline for the Genetic Algorithm (GA) while predicting protein folding. Building blocks containing Hydrophobic (H) -Hydrophilic (P or Polar) covalent bond are utilized such a way that it helps form a core that maximizes the fitness. A series of operators are developed including Diagonal Move and Tilt Move to assist in implementing the building blocks in three-dimensional space. The GGA outperformed Ungers GA in 3D HP model. The overall strategy incorporates a swing function that provides a mechanism to enable the GGA to test more potential solutions and also prevent it from developing a schema that may cause it to become trapped in local minima. Further, it helps the guidelines remain non-rigid. GGA provides improved and robust performance for PFP.

Differential prioritization between relevance and redundancy in correlation-based feature selection techniques for multiclass gene expression data

BackgroundDue to the large number of genes in a typical microarray dataset, feature selection looks set to play an important role in reducing noise and computational cost in gene expression-based tissue classification while improving accuracy at the same time. Surprisingly, this does not appear to be the case for all multiclass microarray datasets. The reason is that many feature selection techniques applied on microarray datasets are either rank-based and hence do not take into account correlations between genes, or are wrapper-based, which require high computational cost, and often yield difficult-to-reproduce results. In studies where correlations between genes are considered, attempts to establish the merit of the proposed techniques are hampered by evaluation procedures which are less than meticulous, resulting in overly optimistic estimates of accuracy.ResultsWe present two realistically evaluated correlation-based feature selection techniques which incorporate, in addition to the two existing criteria involved in forming a predictor set (relevance and redundancy), a third criterion called the degree of differential prioritization (DDP). DDP functions as a parameter to strike the balance between relevance and redundancy, providing our techniques with the novel ability to differentially prioritize the optimization of relevance against redundancy (and vice versa). This ability proves useful in producing optimal classification accuracy while using reasonably small predictor set sizes for nine well-known multiclass microarray datasets.ConclusionFor multiclass microarray datasets, especially the GCM and NCI60 datasets, DDP enables our filter-based techniques to produce accuracies better than those reported in previous studies which employed similarly realistic evaluation procedures.

A new guided genetic algorithm for 2D hydrophobic-hydrophilic model to predict protein folding

This paper presents a novel guided genetic algorithm (GGA) for protein folding prediction (PFP) in 2D hydrophobic-hydrophilic (HP) by exploring the protein core formation concept. A proof of the shape for an optimal core is provided and a set of highly probable sub-conformations are defined which help to establish the guidelines to form the core boundary. A series of new operators including diagonal move and tilt move are defined to assist in implementing the guidelines. The underlying reasons for the failure in the folding prediction of relatively long sequences using Ungers genetic algorithm (GA) in 2D HP model are analysed and the new GGA is shown to overcome these limitations. The overall strategy incorporates a swing function that provides a mechanism to enable the GGA to test more potential solutions and also prevent it from developing a schema that may cause it to become trapped in local minima. While the guidelines do not force particular conformations, the result is a number of conformations for particular putative ground energy and superior prediction accuracy, endorsing the improved performance compared with other well established nondeterministic search approaches

Incorporating time-delays in S-System model for reverse engineering genetic networks

BackgroundIn any gene regulatory network (GRN), the complex interactions occurring amongst transcription factors and target genes can be either instantaneous or time-delayed. However, many existing modeling approaches currently applied for inferring GRNs are unable to represent both these interactions simultaneously. As a result, all these approaches cannot detect important interactions of the other type. S-System model, a differential equation based approach which has been increasingly applied for modeling GRNs, also suffers from this limitation. In fact, all S-System based existing modeling approaches have been designed to capture only instantaneous interactions, and are unable to infer time-delayed interactions.ResultsIn this paper, we propose a novel Time-Delayed S-System (TDSS) model which uses a set of delay differential equations to represent the system dynamics. The ability to incorporate time-delay parameters in the proposed S-System model enables simultaneous modeling of both instantaneous and time-delayed interactions. Furthermore, the delay parameters are not limited to just positive integer values (corresponding to time stamps in the data), but can also take fractional values. Moreover, we also propose a new criterion for model evaluation exploiting the sparse and scale-free nature of GRNs to effectively narrow down the search space, which not only reduces the computation time significantly but also improves model accuracy. The evaluation criterion systematically adapts the max-min in-degrees and also systematically balances the effect of network accuracy and complexity during optimization.ConclusionThe four well-known performance measures applied to the experimental studies on synthetic networks with various time-delayed regulations clearly demonstrate that the proposed method can capture both instantaneous and delayed interactions correctly with high precision. The experiments carried out on two well-known real-life networks, namely IRMA and SOS DNA repair network in Escherichia coli show a significant improvement compared with other state-of-the-art approaches for GRN modeling.

A hybrid genetic algorithm for 2d FCC hydrophobic-hydrophilic lattice model to predict protein folding

This paper presents a Hybrid Genetic Algorithm (HGA) for the protein folding prediction (PFP) applications using the 2D face-centred-cube (FCC) Hydrophobic-Hydrophilic (HP) lattice model. This approach enhances the optimal core formation concept and develops effective and efficient strategies to implement generalized short pull moves to embed highly probable short motifs or building blocks and hence forms the hybridized GA for FCC model. Building blocks containing Hydrophobic (H) – Hydrophilic (P or Polar) covalent bonds are utilized such a way as to help form a core that maximizes the |fitness|. The HGA helps overcome the ineffective crossover and mutation operations that traditionally lead to the stuck condition, especially when the core becomes compact. PFP has been strategically translated into a multi-objective optimization problem and implemented using a swing function, with the HGA providing improved performance in the 2D FCC model compared with the Simple GA.