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.
Factors affecting the organizational adoption of blockchain technology : extending the technology–organization– environment (TOE) framework in the Australian context
Description:
Blockchain technology promises to significantly impact current business processes in industries from various sectors and reduce transactional cost. Firms, suppliers, government, financial institutions etc. are anticipating a business model transformation through blockchain by accomplishing a decentralized architecture of interorganizational dealings without intermediaries. In spite of its immense potential, however, there are key challenges of blockchain implementation which need to be studied for identifying the opportunities arising and for its successful implementations in future. In this paper, we aim to identify these challenges for blockchain adoption and classify them for clearer understanding. To pursue this effectively, this paper follows a hybrid model of systematic literature review. This paper also explicitly enumerates future research opportunities to lead industry and researchers in correct directions
Description:
Blockchain technology promises to significantly impact current business processes in industries from various sectors and reduce transactional cost. Firms, suppliers, government, financial institutions etc. are anticipating a business model transformation through blockchain by accomplishing a decentralized architecture of interorganizational dealings without intermediaries. In spite of its immense potential, however, there are key challenges of blockchain implementation which need to be studied for identifying the opportunities arising and for its successful implementations in future. In this paper, we aim to identify these challenges for blockchain adoption and classify them for clearer understanding. To pursue this effectively, this paper follows a hybrid model of systematic literature review. This paper also explicitly enumerates future research opportunities to lead industry and researchers in correct directions
Description:
Solutions for deriving the most consistent Bayesian gene regulatory network model from given data sets using evolutionary algorithms typically only result in locally optimal solutions.
Description:
A gene regulatory network (GRN) represents a set of genes along with their regulatory interactions. Cellular behavior is driven by genetic level interactions. Dynamics of such systems show nonlinear saturation kinetics which can be best modeled by Michaelis-Menten (MM) and Hill equations. Although MM equation is being widely used for modeling biochemical processes, it has been applied rarely for reverse engineering GRNs. In this paper, we develop a complete framework for a novel model for GRN inference using MM kinetics. A set of coupled equations is first proposed for modeling GRNs. In the coupled model, Michaelis-Menten constant associated with regulation by a gene is made invariant irrespective of the gene being regulated. The parameter estimation of the proposed model is carried out using an evolutionary optimization method, namely, trigonometric differential evolution (TDE). Subsequently, the model is further improved and the regulations of different genes by a given gene are made distinct by allowing varying values of Michaelis-Menten constants for each regulation. Apart from making the model more relevant biologically, the improvement results in a decoupled GRN model with fast estimation of model parameters. Further, to enhance exploitation of the search, we propose a local search algorithm based on hill climbing heuristics. A novel mutation operation is also proposed to avoid population stagnation and premature convergence. Real life benchmark data sets generated in vivo are used for validating the proposed model. Further, we also analyze realistic in silico datasets generated using GeneNetweaver. The comparison of the performance of proposed model with other existing methods shows the potential of the proposed model.
Description:
A gene regulatory network (GRN) represents a set of genes along with their regulatory interactions. Cellular behavior is driven by genetic level interactions. Dynamics of such systems show nonlinear saturation kinetics which can be best modeled by Michaelis-Menten (MM) and Hill equations. Although MM equation is being widely used for modeling biochemical processes, it has been applied rarely for reverse engineering GRNs. In this paper, we develop a complete framework for a novel model for GRN inference using MM kinetics. A set of coupled equations is first proposed for modeling GRNs. In the coupled model, Michaelis-Menten constant associated with regulation by a gene is made invariant irrespective of the gene being regulated. The parameter estimation of the proposed model is carried out using an evolutionary optimization method, namely, trigonometric differential evolution (TDE). Subsequently, the model is further improved and the regulations of different genes by a given gene are made distinct by allowing varying values of Michaelis-Menten constants for each regulation. Apart from making the model more relevant biologically, the improvement results in a decoupled GRN model with fast estimation of model parameters. Further, to enhance exploitation of the search, we propose a local search algorithm based on hill climbing heuristics. A novel mutation operation is also proposed to avoid population stagnation and premature convergence. Real life benchmark data sets generated in vivo are used for validating the proposed model. Further, we also analyze realistic in silico datasets generated using GeneNetweaver. The comparison of the performance of proposed model with other existing methods shows the potential of the proposed model.
Description:
Abstract Background Dynamic Bayesian network (DBN) is among the mainstream approaches for modeling various biological networks, including the gene regulatory network (GRN). Most current methods for learning DBN employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing, which are only able to locate sub-optimal solutions. Further, current DBN applications have essentially been limited to small sized networks. Results To overcome the above difficulties, we introduce here a deterministic global optimization based DBN approach for reverse engineering genetic networks from time course gene expression data. For such DBN models that consist only of inter time slice arcs, we show that there exists a polynomial time algorithm for learning the globally optimal network structure. The proposed approach, named GlobalMIT+, employs the recently proposed information theoretic scoring metric named mutual information test (MIT). GlobalMIT+ is able to learn high-order time delayed genetic interactions, which are common to most biological systems. Evaluation of the approach using both synthetic and real data sets, including a 733 cyanobacterial gene expression data set, shows significantly improved performance over other techniques. Conclusions Our studies demonstrate that deterministic global optimization approaches can infer large scale genetic networks.
Description:
Abstract Background Dynamic Bayesian network (DBN) is among the mainstream approaches for modeling various biological networks, including the gene regulatory network (GRN). Most current methods for learning DBN employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing, which are only able to locate sub-optimal solutions. Further, current DBN applications have essentially been limited to small sized networks. Results To overcome the above difficulties, we introduce here a deterministic global optimization based DBN approach for reverse engineering genetic networks from time course gene expression data. For such DBN models that consist only of inter time slice arcs, we show that there exists a polynomial time algorithm for learning the globally optimal network structure. The proposed approach, named GlobalMIT+, employs the recently proposed information theoretic scoring metric named mutual information test (MIT). GlobalMIT+ is able to learn high-order time delayed genetic interactions, which are common to most biological systems. Evaluation of the approach using both synthetic and real data sets, including a 733 cyanobacterial gene expression data set, shows significantly improved performance over other techniques. Conclusions Our studies demonstrate that deterministic global optimization approaches can infer large scale genetic networks.
Description:
Previous empirical works have shown the effectiveness of differential prioritization in feature selection prior to molecular classification. We now propose to determine the theoretical basis for the concept of differential prioritization through mathematical analyses of the characteristics of predictor sets found using different values of the DDP (degree of differential prioritization) from realistic toy datasets. Mathematical analyses based on analytical measures such as distance between classes are implemented on these predictor sets. We demonstrate that the optimal value of the DDP is capable of forming a predictor set which consists of classes of features which are well separated and are highly correlated to the target classes – a characteristic of a truly optimal predictor set. From these analyses, the necessity of adjusting the DDP based on the dataset of interest is confirmed in a mathematical manner, indicating that the DDP-based feature selection technique is superior to both simplistic rank-based selection and state-of-the-art equal-priorities scoring methods. Applying similar analyses to real-life multiclass microarray datasets, we obtain further proof of the theoretical significance of the DDP for practical applications
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:
Cyanobacteria, a group of photosynthetic prokaryotes, oscillate between day and night time metabolisms with concomitant oscillations in gene expression in response to light/dark cycles (LD). The oscillations in gene expression have been shown to sustain in constant light (LL) with a free running period of 24 h in a model cyanobacterium Synechococcus elongatus PCC 7942. However, equivalent oscillations in metabolism are not reported under LL in this non-nitrogen fixing cyanobacterium. Here we focus on Cyanothece sp. ATCC 51142, a unicellular, nitrogen-fixing cyanobacterium known to temporally separate the processes of oxygenic photosynthesis and oxygen-sensitive nitrogen fixation. In a recent report, metabolism of Cyanothece 51142 has been shown to oscillate between photosynthetic and respiratory phases under LL with free running periods that are temperature dependent but significantly shorter than the circadian period. Further, the oscillations shift to circadian pattern at moderate cell densities that are concomitant with slower growth rates. Here we take this understanding forward and demonstrate that the ultradian rhythm under LL sustains at much higher cell densities when grown under turbulent regimes that simulate flashing light effect. Our results suggest that the ultradian rhythm in metabolism may be needed to support higher carbon and nitrogen requirements of rapidly growing cells under LL. With a comprehensive Real time PCR based gene expression analysis we account for key regulatory interactions and demonstrate the interplay between clock genes and the genes of key metabolic pathways. Further, we observe that several genes that peak at dusk in Synechococcus peak at dawn in Cyanothece and vice versa. The circadian rhythm of this organism appears to be more robust with peaking of genes in anticipation of the ensuing photosynthetic and respiratory metabolic phases.
Description:
Cyanobacteria, a group of photosynthetic prokaryotes, oscillate between day and night time metabolisms with concomitant oscillations in gene expression in response to light/dark cycles (LD). The oscillations in gene expression have been shown to sustain in constant light (LL) with a free running period of 24 h in a model cyanobacterium Synechococcus elongatus PCC 7942. However, equivalent oscillations in metabolism are not reported under LL in this non-nitrogen fixing cyanobacterium. Here we focus on Cyanothece sp. ATCC 51142, a unicellular, nitrogen-fixing cyanobacterium known to temporally separate the processes of oxygenic photosynthesis and oxygen-sensitive nitrogen fixation. In a recent report, metabolism of Cyanothece 51142 has been shown to oscillate between photosynthetic and respiratory phases under LL with free running periods that are temperature dependent but significantly shorter than the circadian period. Further, the oscillations shift to circadian pattern at moderate cell densities that are concomitant with slower growth rates. Here we take this understanding forward and demonstrate that the ultradian rhythm under LL sustains at much higher cell densities when grown under turbulent regimes that simulate flashing light effect. Our results suggest that the ultradian rhythm in metabolism may be needed to support higher carbon and nitrogen requirements of rapidly growing cells under LL. With a comprehensive Real time PCR based gene expression analysis we account for key regulatory interactions and demonstrate the interplay between clock genes and the genes of key metabolic pathways. Further, we observe that several genes that peak at dusk in Synechococcus peak at dawn in Cyanothece and vice versa. The circadian rhythm of this organism appears to be more robust with peaking of genes in anticipation of the ensuing photosynthetic and respiratory metabolic phases.
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:
Proteins are sequences of amino acids bound into a linear chain that adopt a specific folded three-dimensional (3D) shape. This specific folded shape enables proteins to perform specific tasks. The protein structure prediction (PSP) by ab initio or de novo approach is promising amongst various available computational methods and can help to unravel the important relationship between sequence and its corresponding structure. This article presents the ab initio protein structure prediction as a conformational search problem in low resolution model using genetic algorithm. As a review, the essence of twin removal, intelligence in coding, the development and application of domain specific heuristics garnered from the properties of the resulting model and the protein core formation concept discussed are all highly relevant in attempting to secure the best solution.
Description:
Proteins are sequences of amino acids bound into a linear chain that adopt a specific folded three-dimensional (3D) shape. This specific folded shape enables proteins to perform specific tasks. The protein structure prediction (PSP) by ab initio or de novo approach is promising amongst various available computational methods and can help to unravel the important relationship between sequence and its corresponding structure. This article presents the ab initio protein structure prediction as a conformational search problem in low resolution model using genetic algorithm. As a review, the essence of twin removal, intelligence in coding, the development and application of domain specific heuristics garnered from the properties of the resulting model and the protein core formation concept discussed are all highly relevant in attempting to secure the best solution.
Description:
Gene regulatory network (GRN) consists of interactions between transcription factors (TFs) and target genes (TGs). Recently, it has been observed that micro RNAs (miRNAs) play a significant part in genetic interactions. However, current microarray technologies do not capture miRNA expression levels. To overcome this, we propose a new technique to reverse engineer GRN from the available partial microarray data which contains expression levels of TFs and TGs only. Using S-System model, the approach is adapted to cope with the unavailability of information about the expression levels of miRNAs. The versatile Differential Evolutionary algorithm is used for optimization and parameter estimation. Experimental studies on four in silico networks, and a real network of Saccharomyces cerevisiae called IRMA network, show significant improvement compared to traditional S-System approach.
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:
Gene Regulatory Network (GRN) contains interactions occurring between transcription factors (TF) and target genes which are captured during the microarray creation. However, information about the interactions among microRNAs (miRNA) and target genes can not be captured by current microarray technology. To overcome this limitation, we propose a new technique to reverse engineer GRN from partial microarray data which represent target genes' interactions only. Using S-System model, the approach is modified to incorporate the unavailability of information about miRNA-target genes interactions. The most versatile Differential Evolutionary algorithm is used for optimization and parameter learning. Experimental studies on three newly created synthetic networks, and one real network of Saccharomycescerevisiae called IRMA network, show significant improvement compared to traditional S-System based approach.
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.