Description:
Because of the high dimensionality of the microarray data sets, feature selection (FS) has become an important challenge in molecular classification. Using the degree of differential prioritization (DDP) between relevance and antiredundancy, our proposed DDP-based FS technique is capable of achieving better accuracies than those previously reported, using a smaller predictor set. However, previously, we have neither devised nor used any method for determining the value of the DDP to be used for the data set of interest before the FS process. In this article, we propose a system for predicting the optimal value of the DDP, which costs less computationally than conventional tuning while maintaining the independence of the FS technique from the type of underlying classifier used
Description:
This chapter presents modelling gene regulatory networks (GRNs) using probabilistic causal model and the guided genetic algorithm. The problem of modelling is explained from both a biological and computational perspective. Further, a comprehensive methodology for developing a GRN model is presented where the application of computation intelligence (CI) techniques can be seen to be significantly important in each phase of modelling. An illustrative example of the causal model for GRN modelling is also included and applied to model the yeast cell cycle dataset. The results obtained are compared for providing biological relevance to the findings which thereby underpins the CI based modelling techniques.
Description:
Inferring the gene regulatory network (GRN) structure from data is an important problem in computational biology. However, it is a computationally complex problem and approximate methods such as heuristic search techniques, restriction of the maximum-number-of-parents (maxP) for a gene, or an optimal search under special conditions are required. The limitations of a heuristic search are well known but literature on the detailed analysis of the widely used maxP technique is lacking. The optimal search methods require large computational time. We report the theoretical analysis and experimental results of the strengths and limitations of the maxP technique. Further, using an optimal search method, we combine the strengths of the maxP technique and the known GRN topology to propose two novel algorithms. These algorithms are implemented in a Bayesian network framework and tested on biological, realistic, and in silico networks of different sizes and topologies. They overcome the limitations of the maxP technique and show superior computational speed when compared to the current optimal search algorithms.
Description:
Nondeterministic conformational search techniques, such as Genetic Algorithms (GAs) are promising for solving protein structure prediction (PSP) problem. The crossover operator of a GA can underpin the formation of potential conformations by exchanging and sharing potential sub-conformations, which is promising for solving PSP. However, the usual nature of an optimum PSP conformation being compact can produce many invalid conformations (by having non-self-avoiding-walk) using crossover. While a crossover-based converging conformation suffers from limited pathways, combining it with depth-first search (DFS) can partially reveal potential pathways. DFS generates random conformations increasingly quickly with increasing length of the protein sequences compared to random-move-only-based conformation generation. Random conformations are frequently applied for maintaining diversity as well as for initialization in many GA variations.
Description:
Nondeterministic conformational search techniques, such as Genetic Algorithms (GAs) are promising for solving protein structure prediction (PSP) problem. The crossover operator of a GA can underpin the formation of potential conformations by exchanging and sharing potential sub-conformations, which is promising for solving PSP. However, the usual nature of an optimum PSP conformation being compact can produce many invalid conformations (by having non-self-avoiding-walk) using crossover. While a crossover-based converging conformation suffers from limited pathways, combining it with depth-first search (DFS) can partially reveal potential pathways. DFS generates random conformations increasingly quickly with increasing length of the protein sequences compared to random-move-only-based conformation generation. Random conformations are frequently applied for maintaining diversity as well as for initialization in many GA variations.
Description:
Background: Understanding gene interactions is a fundamental question in systems biology. Currently, modeling of gene regulations using the Bayesian Network (BN) formalism assumes that genes interact either instantaneously or with a certain amount of time delay. However in reality, biological regulations, both instantaneous and time-delayed, occur simultaneously. A framework that can detect and model both these two types of interactions simultaneously would represent gene regulatory networks more accurately. Results: In this paper, we introduce a framework based on the Bayesian Network (BN) formalism that can represent both instantaneous and time-delayed interactions between genes simultaneously. A novel scoring metric having firm mathematical underpinnings is also proposed that, unlike other recent methods, can score both interactions concurrently and takes into account the reality that multiple regulators can regulate a gene jointly, rather than in an isolated pair-wise manner. Further, a gene regulatory network (GRN) inference method employing an evolutionary search that makes use of the framework and the scoring metric is also presented. Conclusion: By taking into consideration the biological fact that both instantaneous and time-delayed regulations can occur among genes, our approach models gene interactions with greater accuracy. The proposed framework is efficient and can be used to infer gene networks having multiple orders of instantaneous and time-delayed regulations simultaneously. Experiments are carried out using three different synthetic networks (with three different mechanisms for generating synthetic data) as well as real life networks of Saccharomyces cerevisiae, E. coli and cyanobacteria gene expression data. The results show the effectiveness of our approach.
Description:
Background: Understanding gene interactions is a fundamental question in systems biology. Currently, modeling of gene regulations using the Bayesian Network (BN) formalism assumes that genes interact either instantaneously or with a certain amount of time delay. However in reality, biological regulations, both instantaneous and time-delayed, occur simultaneously. A framework that can detect and model both these two types of interactions simultaneously would represent gene regulatory networks more accurately. Results: In this paper, we introduce a framework based on the Bayesian Network (BN) formalism that can represent both instantaneous and time-delayed interactions between genes simultaneously. A novel scoring metric having firm mathematical underpinnings is also proposed that, unlike other recent methods, can score both interactions concurrently and takes into account the reality that multiple regulators can regulate a gene jointly, rather than in an isolated pair-wise manner. Further, a gene regulatory network (GRN) inference method employing an evolutionary search that makes use of the framework and the scoring metric is also presented. Conclusion: By taking into consideration the biological fact that both instantaneous and time-delayed regulations can occur among genes, our approach models gene interactions with greater accuracy. The proposed framework is efficient and can be used to infer gene networks having multiple orders of instantaneous and time-delayed regulations simultaneously. Experiments are carried out using three different synthetic networks (with three different mechanisms for generating synthetic data) as well as real life networks of Saccharomyces cerevisiae, E. coli and cyanobacteria gene expression data. The results show the effectiveness of our approach.
Description:
Abstract—Gene Regulatory Network (GRN) plays an important role in the understanding of complex biological systems. In most cases, high throughput microarray gene expression data is used for finding these regulatory relationships among genes. In this paper, we present a novel approach, based on decoupled SSystem model, for reverse engineering GRNs. In the proposed method, the genetic algorithm used for scoring the networks contains several useful features for accurate network inference, namely a Prediction Initialization (PI) algorithm to initialize the individuals, a Flip Operation (FO) for better mating of values and a restricted execution of Hill Climbing Local Search over few individuals. It also includes a novel refinement technique which utilizes the fit solutions of the genetic algorithm for optimizing sensitivity and specificity of the inferred network. Comparative studies and robustness analysis using standard benchmark data set show the superiority of the proposed method.
Coupling of cellular processes and their coordinated oscillations under continuous light in Cyanothece sp. ATCC 51142, a diazotrophic unicellular cyanobacterium
Description:
A holistic understanding of genetic interactions is crucial in the analysis of complex biological systems. However, due to the dimensionality problem (less samples and large number of genes) of microarray data, obtaining an optimal gene regulatory network is not only difficult but also computationally expensive. In this paper, a Bayesian model for the genetic interactions using the Minimum Description Length as a scoring metric is proposed. For fast optimisation of the network structure, we propose a novel Swarm Intelligence algorithm called Binary-Organoid Particle Swarm (BORG-Swarm). In BORG-Swarm we introduce the concepts of probability threshold vector and particle drift to update particle positions. Experimental studies are carried out using real-life yeast cell cycle dataset. Results indicate that existing binary swarms fail to converge and suffer from long runtimes. In constrast, BORG-Swarm's fast convergence towards the global optimum becomes apparent from results of extensive simulations.
Description:
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.
Description:
In this paper, we propose novel algorithmic models based on fusion of independent and correlated gene features for multiclass microarray gene expression classification. It is possible for genes to get co-expressed via different pathways. Moreover, a gene may or may not be co-active for all samples. In this paper, we approach this problem with a optimal feature selection technique using analysis based on statistical techniques to model the complex interactions between genes. The two different types of correlation modelling techniques based on the cross modal factor analysis (CFA) and canonical correlation analysis (CCA) were examined. The subsequent fusion of CCA/CFA features with principal component analysis (PCA) features at feature-level, and at score-level result in significant enhancement in classification accuracy for different data sets corresponding to multiclass microarray gene expression data.
Description:
In this paper a novel feature selection technique based on mutual dependency modelling between genes is proposed for multiclass microarray gene expression classification. Several studies on analysis of gene expression data has shown that the genes (whether or not they belong to the same gene group) get co-expressed via a variety of pathways. Further, a gene may participate in multiple pathways that may or may not be co-active for all samples. It is therefore biologically meaningful to simultaneously divide genes into functional groups and samples into co-active categories. This can be done by modeling gene profiles for multiclass microarray gene data sets based on mutual dependency models, which model complex gene interactions. Most of the current works in multiclass microarray gene expression studies are based on statistical models with little or no consideration of gene interactions. This has led to lack of robustness and overly optimistic estimates of accuracy and noise reduction. In this paper, we propose multivariate analysis techniques which model the mutual dependency between the features and take into account complex interactions for extracting a subset of genes. The two techniques, the cross modal factor analysis (CFA) and canonical correlation analysis(CCA) show a significant reduction in dimensionality and class-prediction error, and improvement in classification accuracy for multiclass microarray gene expression datasets.
Description:
Dynamic Bayesian networks (DBN) are widely applied in Systems biology for modeling various biological networks, including gene regulatory networks and metabolic networks. The application of DBN models often requires data discretization. Although various discretization techniques exist, currently there is no consensus on which approach is most suitable. Popular discretization strategies within the bioinformatics community, such as interval and quantile discretization, are likely not optimal. In this paper, we propose a novel approach for data discretization for mutual information based learning of DBN. In this approach, the data are discretized so that the mutual information between parent and child nodes is maximized, subject to a suitable penalty put on the complexity of the discretization. A dynamic programming approach is used to find the optimal discretization threshold for each individual variable. Our approach iteratively learns both the network and the discretization scheme until a locally optimal solution is reached. Tests on real genetic networks confirm the effectiveness of the proposed method.
Description:
Genetic network reverse engineering has been an area of intensive research within the systems biology community during the last decade. With many techniques currently available, the task of validating them and choosing the best one for a certain problem is a complex issue. Current practice has been to validate an approach on in-silico synthetic data sets, and, wherever possible, on real data sets with known ground-truth. In this study, we highlight a major issue that the validation of reverse engineering algorithms on small benchmark networks very often results in networks which are not statistically better than a randomly picked network. Another important issue highlighted is that with short time series, a small variation in the pre-processing procedure might yield large differences in the inferred networks. To demonstrate these issues, we have selected as our case study the IRMA in-vivo synthetic yeast network recently published in Cell. Using Fisher's exact test, we show that many results reported in the literature on reverse-engineering this network are not significantly better than random. The discussion is further extended to some other networks commonly used for validation purposes in the literature. The results presented in this study emphasize that studies carried out using small genetic networks are likely to be trivial, making it imperative that larger real networks be used for validating and benchmarking purposes. If smaller networks are considered, then the results should be interpreted carefully to avoid over confidence. This article is part of a Special Issue entitled: Computational Methods for Protein Interaction and Structural Prediction.
Description:
Protein Structure Prediction (PSP) is a challenging optimization problem in computational biology. A large number of non-deterministic approaches such as Evolutionary Algorithms (EAs) have been have been effectively applied to a variety of fields though, in the rugged landscape of multimodal problem like PSP, it can perform unsatisfactorily, due to premature convergence. In EAs, selection plays a significant role to avoid getting trapped in local optima and also to guide the evolution towards an optimal solution. In this paper, we propose a new Sib-based survival selection strategy suitable for application in a genetic algorithm (GA) to deal with multimodal problems. The proposed strategy, inspired by the concept of crowding method, controls the flow of genetic material by pairing off the fittest offspring amongst all the sibs (offspring inheriting most of the genetic material from an ancestor) with its ancestor for survival. Furthermore, by selecting the survivors in a hybridized manner of deterministic and probabilistic selection, the method allows the exploitation of less fit solutions along with the fitter ones and thus facilitates escaping from local optima (minima in case of PSP). Experiments conducted on a set of widely used benchmark sequences for 3D-FCC HP lattice model, demonstrate the potential of the proposed method, both in terms of diversity and optimal energy in regard to various state-of-the-art selection methods.
Description:
A holistic understanding of genetic interactions, in the post-genomic era, is vital for analysing complex biological systems. In this paper, we present an information theory based novel gene regulatory network inference method using the dynamic Bayesian network (DBN) framework. The proposed approach, with strong theoretical underpinnings, employs mutual information based conditional independence tests to assess the regulatory relationships among genes. The method is flexible, computationally fast and allows a-priori incorporation of biological domain knowledge. We apply it to the analysis of synthetic data as well as Saccharomyces cerevisiae (yeast cell cycle) gene expression data. Performance measures applied to simulation studies show the superior performance of the proposed method
Description:
Understanding gene interactions is a fundamental question in systems biology. Currently, modeling of gene regulations assumes that genes interact either instantaneously or with time delay. In this paper, we introduce a framework based on the Bayesian Network (BN) formalism that can represent both instantaneous and time-delayed interactions between genes simultaneously. Also, a novel scoring metric having firm mathematical underpinnings is then proposed that, unlike other recent methods, can score both interactions concurrently and takes into account the biological fact that multiple regulators may regulate a gene jointly, rather than in an isolated pair-wise manner. Further, a gene regulatory network inference method employing evolutionary search that makes use of the framework and the scoring metric is also presented. Experiments carried out using synthetic data as well as the well known Saccharomyces cerevisiae gene expression data show the effectiveness of our approach.
Description:
Predicting the minimum energy protein structure from its amino acid sequence, even under the rather simplified HP lattice model, continues to be an important and challenging problem in computational biology. In this paper, we propose a novel initial population generation strategy for evolutionary algorithm incorporating domain knowledge based on the concept of maximum hydrophobic core formation for Protein structure prediction (PSP) problem. The proposed technique helps the optimization process to commence with diverse seeds and thereby aids in converging to the global solution quickly. The experimental results, conducted on PSP problem using HP benchmark sequences for 2D square and 3D cubic lattice model, demonstrate that the proposed evolutionary algorithm with new core-based population initialization technique is very effective in improving the optimization process in terms of convergence as well as in achieving the optimal energy.