Rhythmic and sustained oscillations in metabolism and gene expression of Cyanothece sp. ATCC 51142 under constant light
- Gaudana, Sandeep, Krishnakumar, S., Alagesan, Swathi, Digmurti, Madhuri, Viswanathan, Ganesh, Chetty, Madhu, Wangikar, Pramod
- Authors: Gaudana, Sandeep , Krishnakumar, S. , Alagesan, Swathi , Digmurti, Madhuri , Viswanathan, Ganesh , Chetty, Madhu , Wangikar, Pramod
- Date: 2013
- Type: Text , Journal article
- Relation: Frontiers in Microbiology Vol. 4, no. Article 374 (2013), p. 1-11
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- 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.
- Authors: Gaudana, Sandeep , Krishnakumar, S. , Alagesan, Swathi , Digmurti, Madhuri , Viswanathan, Ganesh , Chetty, Madhu , Wangikar, Pramod
- Date: 2013
- Type: Text , Journal article
- Relation: Frontiers in Microbiology Vol. 4, no. Article 374 (2013), p. 1-11
- Full Text:
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- 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.
Gene regulatory network modeling via global optimization of high-order dynamic Bayesian network
- Nguyen, Vinh, Chetty, Madhu, Coppel, Ross, Wangikar, Pramod
- Authors: Nguyen, Vinh , Chetty, Madhu , Coppel, Ross , Wangikar, Pramod
- Date: 2012
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 13, no. 131 (2012), p. 1-16
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- 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.
- Authors: Nguyen, Vinh , Chetty, Madhu , Coppel, Ross , Wangikar, Pramod
- Date: 2012
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 13, no. 131 (2012), p. 1-16
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- 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.
Hidden Markov models Incorporating fuzzy measures and integrals for protein sequence identification and alignment
- Bidargaddi, Niranjan, Chetty, Madhu, Kamruzzaman, Joarder
- Authors: Bidargaddi, Niranjan , Chetty, Madhu , Kamruzzaman, Joarder
- Date: 2008
- Type: Text , Journal article
- Relation: Genomics Proteomics & Bioinformatics Vol. 6, no. 2 (2008), p.98–110
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- Description: 2014060227
- Authors: Bidargaddi, Niranjan , Chetty, Madhu , Kamruzzaman, Joarder
- Date: 2008
- Type: Text , Journal article
- Relation: Genomics Proteomics & Bioinformatics Vol. 6, no. 2 (2008), p.98–110
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- Description: 2014060227
A model of the circadian clock in the cyanobacterium Cyanothece sp. ATCC 51142
- Nguyen, Vinh, Chetty, Madhu, Coppel, Ross, Gaudana, Sandeep, Wangikar, Pramod
- Authors: Nguyen, Vinh , Chetty, Madhu , Coppel, Ross , Gaudana, Sandeep , Wangikar, Pramod
- Date: 2013
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 14, no. (Supplement 2) (2013), p. s14-1-s14-9
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- Description: Background The over consumption of fossil fuels has led to growing concerns over climate change and global warming. Increasing research activities have been carried out towards alternative viable biofuel sources. Of several different biofuel platforms, cyanobacteria possess great potential, for their ability to accumulate biomass tens of times faster than traditional oilseed crops. The cyanobacterium Cyanothece sp. ATCC 51142 has recently attracted lots of research interest as a model organism for such research. Cyanothece can perform efficiently both photosynthesis and nitrogen fixation within the same cell, and has been recently shown to produce biohydrogen--a byproduct of nitrogen fixation--at very high rates of several folds higher than previously described hydrogen-producing photosynthetic microbes. Since the key enzyme for nitrogen fixation is very sensitive to oxygen produced by photosynthesis, Cyanothece employs a sophisticated temporal separation scheme, where nitrogen fixation occurs at night and photosynthesis at day. At the core of this temporal separation scheme is a robust clocking mechanism, which so far has not been thoroughly studied. Understanding how this circadian clock interacts with and harmonizes global transcription of key cellular processes is one of the keys to realize the inherent potential of this organism. Results In this paper, we employ several state of the art bioinformatics techniques for studying the core circadian clock in Cyanothece sp. ATCC 51142, and its interactions with other key cellular processes. We employ comparative genomics techniques to map the circadian clock genes and genetic interactions from another cyanobacterial species, namely Synechococcus elongatus PCC 7942, of which the circadian clock has been much more thoroughly investigated. Using time series gene expression data for Cyanothece, we employ gene regulatory network reconstruction techniques to learn this network de novo, and compare the reconstructed network against the interactions currently reported in the literature. Next, we build a computational model of the interactions between the core clock and other cellular processes, and show how this model can predict the behaviour of the system under changing environmental conditions. The constructed models significantly advance our understanding of the Cyanothece circadian clock functional mechanisms.
- Authors: Nguyen, Vinh , Chetty, Madhu , Coppel, Ross , Gaudana, Sandeep , Wangikar, Pramod
- Date: 2013
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 14, no. (Supplement 2) (2013), p. s14-1-s14-9
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- Description: Background The over consumption of fossil fuels has led to growing concerns over climate change and global warming. Increasing research activities have been carried out towards alternative viable biofuel sources. Of several different biofuel platforms, cyanobacteria possess great potential, for their ability to accumulate biomass tens of times faster than traditional oilseed crops. The cyanobacterium Cyanothece sp. ATCC 51142 has recently attracted lots of research interest as a model organism for such research. Cyanothece can perform efficiently both photosynthesis and nitrogen fixation within the same cell, and has been recently shown to produce biohydrogen--a byproduct of nitrogen fixation--at very high rates of several folds higher than previously described hydrogen-producing photosynthetic microbes. Since the key enzyme for nitrogen fixation is very sensitive to oxygen produced by photosynthesis, Cyanothece employs a sophisticated temporal separation scheme, where nitrogen fixation occurs at night and photosynthesis at day. At the core of this temporal separation scheme is a robust clocking mechanism, which so far has not been thoroughly studied. Understanding how this circadian clock interacts with and harmonizes global transcription of key cellular processes is one of the keys to realize the inherent potential of this organism. Results In this paper, we employ several state of the art bioinformatics techniques for studying the core circadian clock in Cyanothece sp. ATCC 51142, and its interactions with other key cellular processes. We employ comparative genomics techniques to map the circadian clock genes and genetic interactions from another cyanobacterial species, namely Synechococcus elongatus PCC 7942, of which the circadian clock has been much more thoroughly investigated. Using time series gene expression data for Cyanothece, we employ gene regulatory network reconstruction techniques to learn this network de novo, and compare the reconstructed network against the interactions currently reported in the literature. Next, we build a computational model of the interactions between the core clock and other cellular processes, and show how this model can predict the behaviour of the system under changing environmental conditions. The constructed models significantly advance our understanding of the Cyanothece circadian clock functional mechanisms.
Reverse engineering genetic networks using nonlinear saturation kinetics
- Youseph, Ahammed, Chetty, Madhu, Karmakar, Gour
- Authors: Youseph, Ahammed , Chetty, Madhu , Karmakar, Gour
- Date: 2019
- Type: Text , Journal article
- Relation: BioSystems Vol. 182, no. (2019), p. 30-41
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- 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.
- Authors: Youseph, Ahammed , Chetty, Madhu , Karmakar, Gour
- Date: 2019
- Type: Text , Journal article
- Relation: BioSystems Vol. 182, no. (2019), p. 30-41
- Full Text:
- Reviewed:
- 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.
Incorporating time-delays in S-System model for reverse engineering genetic networks
- Chowdhury, Ahsan, Chetty, Madhu, Nguyen, Vinh
- Authors: Chowdhury, Ahsan , Chetty, Madhu , Nguyen, Vinh
- Date: 2013
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 14, no. (2013), p. 1-22
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- Description: Background In 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. Results In 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. Conclusion The 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.
- Authors: Chowdhury, Ahsan , Chetty, Madhu , Nguyen, Vinh
- Date: 2013
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 14, no. (2013), p. 1-22
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- Description: Background In 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. Results In 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. Conclusion The 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.
Simultaneous learning of instantaneous and time-delayed genetic interactions using novel information theoretic scoring technique
- Morshed, Nizamul, Chetty, Madhu, Nguyen, Vinh
- Authors: Morshed, Nizamul , Chetty, Madhu , Nguyen, Vinh
- Date: 2012
- Type: Text , Journal article
- Relation: BMC systems biology Vol. 6, no. 62 (2012), p. 62
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- 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.
- Authors: Morshed, Nizamul , Chetty, Madhu , Nguyen, Vinh
- Date: 2012
- Type: Text , Journal article
- Relation: BMC systems biology Vol. 6, no. 62 (2012), p. 62
- Full Text:
- Reviewed:
- 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.
Coupling of cellular processes and their coordinated oscillations under continuous light in Cyanothece sp. ATCC 51142, a diazotrophic unicellular cyanobacterium
- Krishnakumar, Sujatha, Gaudana, Sandeep, Vinh, Nguyen, Viswanathan, Ganesh, Chetty, Madhu, Wangikar, Pramod
- Authors: Krishnakumar, Sujatha , Gaudana, Sandeep , Vinh, Nguyen , Viswanathan, Ganesh , Chetty, Madhu , Wangikar, Pramod
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 10, no. 5 (2015), p. 1-23
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- Description: Unicellular diazotrophic cyanobacteria such as Cyanothece sp. ATCC 51142 (henceforth Cyanothece), temporally separate the oxygen sensitive nitrogen fixation from oxygen evolving photosynthesis not only under diurnal cycles (LD) but also in continuous light (LL). However, recent reports demonstrate that the oscillations in LL occur with a shorter cycle time of ∼11 h. We find that indeed, majority of the genes oscillate in LL with this cycle time. Genes that are upregulated at a particular time of day under diurnal cycle also get upregulated at an equivalent metabolic phase under LL suggesting tight coupling of various cellular events with each other and with the cell's metabolic status. A number of metabolic processes get upregulated in a coordinated fashion during the respiratory phase under LL including glycogen degradation, glycolysis, oxidative pentose phosphate pathway, and tricarboxylic acid cycle. These precede nitrogen fixation apparently to ensure sufficient energy and anoxic environment needed for the nitrogenase enzyme. Photosynthetic phase sees upregulation of photosystem II, carbonate transport, carbon concentrating mechanism, RuBisCO, glycogen synthesis and light harvesting antenna pigment biosynthesis. In Synechococcus elongates PCC 7942, a non-nitrogen fixing cyanobacteria, expression of a relatively smaller fraction of genes oscillates under LL condition with the major periodicity being 24 h. In contrast, the entire cellular machinery of Cyanothece orchestrates coordinated oscillation in anticipation of the ensuing metabolic phase in both LD and LL. These results may have important implications in understanding the timing of various cellular events and in engineering cyanobacteria for biofuel production. © 2015 Krishnakumar et al.
- Authors: Krishnakumar, Sujatha , Gaudana, Sandeep , Vinh, Nguyen , Viswanathan, Ganesh , Chetty, Madhu , Wangikar, Pramod
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 10, no. 5 (2015), p. 1-23
- Full Text:
- Reviewed:
- Description: Unicellular diazotrophic cyanobacteria such as Cyanothece sp. ATCC 51142 (henceforth Cyanothece), temporally separate the oxygen sensitive nitrogen fixation from oxygen evolving photosynthesis not only under diurnal cycles (LD) but also in continuous light (LL). However, recent reports demonstrate that the oscillations in LL occur with a shorter cycle time of ∼11 h. We find that indeed, majority of the genes oscillate in LL with this cycle time. Genes that are upregulated at a particular time of day under diurnal cycle also get upregulated at an equivalent metabolic phase under LL suggesting tight coupling of various cellular events with each other and with the cell's metabolic status. A number of metabolic processes get upregulated in a coordinated fashion during the respiratory phase under LL including glycogen degradation, glycolysis, oxidative pentose phosphate pathway, and tricarboxylic acid cycle. These precede nitrogen fixation apparently to ensure sufficient energy and anoxic environment needed for the nitrogenase enzyme. Photosynthetic phase sees upregulation of photosystem II, carbonate transport, carbon concentrating mechanism, RuBisCO, glycogen synthesis and light harvesting antenna pigment biosynthesis. In Synechococcus elongates PCC 7942, a non-nitrogen fixing cyanobacteria, expression of a relatively smaller fraction of genes oscillates under LL condition with the major periodicity being 24 h. In contrast, the entire cellular machinery of Cyanothece orchestrates coordinated oscillation in anticipation of the ensuing metabolic phase in both LD and LL. These results may have important implications in understanding the timing of various cellular events and in engineering cyanobacteria for biofuel production. © 2015 Krishnakumar et al.
PCA based population generation for genetic network optimization
- Youseph, Ahammed, Chetty, Madhu, Karmakar, Gour
- Authors: Youseph, Ahammed , Chetty, Madhu , Karmakar, Gour
- Date: 2018
- Type: Text , Journal article
- Relation: Cognitive Neurodynamics Vol. 12, no. 4 (2018), p. 417-429
- Full Text:
- Reviewed:
- Description: A gene regulatory network (GRN) represents a set of genes and its regulatory interactions. The inference of the regulatory interactions between genes is usually carried out using an appropriate mathematical model and the available gene expression profile. Among the various models proposed for GRN inference, our recently proposed Michaelis–Menten based ODE model provides a good trade-off between the computational complexity and biological relevance. This model, like other known GRN models, also uses an evolutionary algorithm for parameter estimation. Considering various issues associated with such population based stochastic optimization approaches (e.g. diversity, premature convergence due to local optima, accuracy, etc.), it becomes important to seed the initial population with good individuals which are closer to the optimal solution. In this paper, we exploit the inherent strength of principal component analysis (PCA) in a novel manner to initialize the population for GRN optimization. The benefit of the proposed method is validated by reconstructing in silico and in vivo networks of various sizes. For the same level of accuracy, the approach with PCA based initialization shows improved convergence speed.
- Authors: Youseph, Ahammed , Chetty, Madhu , Karmakar, Gour
- Date: 2018
- Type: Text , Journal article
- Relation: Cognitive Neurodynamics Vol. 12, no. 4 (2018), p. 417-429
- Full Text:
- Reviewed:
- Description: A gene regulatory network (GRN) represents a set of genes and its regulatory interactions. The inference of the regulatory interactions between genes is usually carried out using an appropriate mathematical model and the available gene expression profile. Among the various models proposed for GRN inference, our recently proposed Michaelis–Menten based ODE model provides a good trade-off between the computational complexity and biological relevance. This model, like other known GRN models, also uses an evolutionary algorithm for parameter estimation. Considering various issues associated with such population based stochastic optimization approaches (e.g. diversity, premature convergence due to local optima, accuracy, etc.), it becomes important to seed the initial population with good individuals which are closer to the optimal solution. In this paper, we exploit the inherent strength of principal component analysis (PCA) in a novel manner to initialize the population for GRN optimization. The benefit of the proposed method is validated by reconstructing in silico and in vivo networks of various sizes. For the same level of accuracy, the approach with PCA based initialization shows improved convergence speed.
Factors affecting the organizational adoption of blockchain technology : extending the technology–organization– environment (TOE) framework in the Australian context
- Malik, Saleem, Chadhar, Mehmood, Vatanasakdakul, Savanid, Chetty, Madhu
- Authors: Malik, Saleem , Chadhar, Mehmood , Vatanasakdakul, Savanid , Chetty, Madhu
- Date: 2021
- Type: Text , Journal article
- Relation: Sustainability (Switzerland) Vol. 13, no. 16 (2021), p.
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- Description: Blockchain technology (BCT) has been gaining popularity due to its benefits for almost every industry. However, despite its benefits, the organizational adoption of BCT is rather limited. This lack of uptake motivated us to identify the factors that influence the adoption of BCT from an organizational perspective. In doing this, we reviewed the BCT literature, interviewed BCT experts, and proposed a research model based on the TOE framework. Specifically, we theorized the role of technological (perceived benefits, compatibility, information transparency, and disintermediation), organizational (organization innovativeness, organizational learning capability, and top management support), and environmental (competition intensity, government support, trading partners readiness, and standards uncertainty) factors in the organizational adoption of BCT in Australia. We confirmed the model with a sample of adopters and potential adopter organizations in Aus-tralia. The results show a significant role of the proposed factors in the organizational adoption of BCT in Australia. Additionally, we found that the relationship between the influential factors and BCT adoption is moderated by “perceived risks”. The study extends the TOE framework by adding factors that were ignored in previous studies on BCT adoption, such as perceived information trans-parency, perceived disintermediation, organizational innovativeness, organizational learning capa-bility, and standards uncertainty. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Authors: Malik, Saleem , Chadhar, Mehmood , Vatanasakdakul, Savanid , Chetty, Madhu
- Date: 2021
- Type: Text , Journal article
- Relation: Sustainability (Switzerland) Vol. 13, no. 16 (2021), p.
- Full Text:
- Reviewed:
- Description: Blockchain technology (BCT) has been gaining popularity due to its benefits for almost every industry. However, despite its benefits, the organizational adoption of BCT is rather limited. This lack of uptake motivated us to identify the factors that influence the adoption of BCT from an organizational perspective. In doing this, we reviewed the BCT literature, interviewed BCT experts, and proposed a research model based on the TOE framework. Specifically, we theorized the role of technological (perceived benefits, compatibility, information transparency, and disintermediation), organizational (organization innovativeness, organizational learning capability, and top management support), and environmental (competition intensity, government support, trading partners readiness, and standards uncertainty) factors in the organizational adoption of BCT in Australia. We confirmed the model with a sample of adopters and potential adopter organizations in Aus-tralia. The results show a significant role of the proposed factors in the organizational adoption of BCT in Australia. Additionally, we found that the relationship between the influential factors and BCT adoption is moderated by “perceived risks”. The study extends the TOE framework by adding factors that were ignored in previous studies on BCT adoption, such as perceived information trans-parency, perceived disintermediation, organizational innovativeness, organizational learning capa-bility, and standards uncertainty. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
From general language understanding to noisy text comprehension
- Kasthuriarachchy, Buddhika, Chetty, Madhu, Shatte, Adrian, Walls, Darren
- Authors: Kasthuriarachchy, Buddhika , Chetty, Madhu , Shatte, Adrian , Walls, Darren
- Date: 2021
- Type: Text , Journal article
- Relation: Applied Sciences (Switzerland) Vol. 11, no. 17 (2021), p.
- Full Text:
- Reviewed:
- Description: Obtaining meaning-rich representations of social media inputs, such as Tweets (unstructured and noisy text), from general-purpose pre-trained language models has become challenging, as these inputs typically deviate from mainstream English usage. The proposed research establishes effective methods for improving the comprehension of noisy texts. For this, we propose a new generic methodology to derive a diverse set of sentence vectors combining and extracting various linguistic characteristics from latent representations of multi-layer, pre-trained language models. Further, we clearly establish how BERT, a state-of-the-art pre-trained language model, comprehends the linguistic attributes of Tweets to identify appropriate sentence representations. Five new probing tasks are developed for Tweets, which can serve as benchmark probing tasks to study noisy text comprehension. Experiments are carried out for classification accuracy by deriving the sentence vectors from GloVe-based pre-trained models and Sentence-BERT, and by using different hidden layers from the BERT model. We show that the initial and middle layers of BERT have better capability for capturing the key linguistic characteristics of noisy texts than its latter layers. With complex predictive models, we further show that the sentence vector length has lesser importance to capture linguistic information, and the proposed sentence vectors for noisy texts perform better than the existing state-of-the-art sentence vectors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Authors: Kasthuriarachchy, Buddhika , Chetty, Madhu , Shatte, Adrian , Walls, Darren
- Date: 2021
- Type: Text , Journal article
- Relation: Applied Sciences (Switzerland) Vol. 11, no. 17 (2021), p.
- Full Text:
- Reviewed:
- Description: Obtaining meaning-rich representations of social media inputs, such as Tweets (unstructured and noisy text), from general-purpose pre-trained language models has become challenging, as these inputs typically deviate from mainstream English usage. The proposed research establishes effective methods for improving the comprehension of noisy texts. For this, we propose a new generic methodology to derive a diverse set of sentence vectors combining and extracting various linguistic characteristics from latent representations of multi-layer, pre-trained language models. Further, we clearly establish how BERT, a state-of-the-art pre-trained language model, comprehends the linguistic attributes of Tweets to identify appropriate sentence representations. Five new probing tasks are developed for Tweets, which can serve as benchmark probing tasks to study noisy text comprehension. Experiments are carried out for classification accuracy by deriving the sentence vectors from GloVe-based pre-trained models and Sentence-BERT, and by using different hidden layers from the BERT model. We show that the initial and middle layers of BERT have better capability for capturing the key linguistic characteristics of noisy texts than its latter layers. With complex predictive models, we further show that the sentence vector length has lesser importance to capture linguistic information, and the proposed sentence vectors for noisy texts perform better than the existing state-of-the-art sentence vectors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Towards machine learning approach for digital-health intervention program
- Santhanagopalan, Meena, Chetty, Madhu, Foale, Cameron, Klein, Britt
- Authors: Santhanagopalan, Meena , Chetty, Madhu , Foale, Cameron , Klein, Britt
- Date: 2019
- Type: Text , Journal article
- Relation: Australian Journal of Intelligent Information Processing System Vol. 15, no. 4 (2019), p. 16-24
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- Description: Digital-Health intervention (DHI) are used by health care providers to promote engagement within community. Effective assignment of participants into DHI programs helps increasing benefits from the most suitable intervention. A major challenge with the roll-out and implementation of DHI, is in assigning participants into different interventions. The use of biopsychosocial model [18] for this purpose is not wide spread, due to limited personalized interventions formed on evidence-based data-driven models. Machine learning has changed the way data extraction and interpretation works by involving automatic sets of generic methods that have replaced the traditional statistical techniques. In this paper, we propose to investigate relevance of machine learning for this purpose and is carried out by studying different non-linear classifiers and compare their prediction accuracy to evaluate their suitability. Further, as a novel contribution, real-life biopsychosocial features are used as input in this study. The results help in developing an appropriate predictive classication model to assign participants into the most suitable DHI. We analyze biopsychosocial data generated from a DHI program and study their feature characteristics using scatter plots. While scatter plots are unable to reveal the linear relationships in the data-set, the use of classifiers can successfully identify which features are suitable predictors of mental ill health.
- Authors: Santhanagopalan, Meena , Chetty, Madhu , Foale, Cameron , Klein, Britt
- Date: 2019
- Type: Text , Journal article
- Relation: Australian Journal of Intelligent Information Processing System Vol. 15, no. 4 (2019), p. 16-24
- Full Text:
- Reviewed:
- Description: Digital-Health intervention (DHI) are used by health care providers to promote engagement within community. Effective assignment of participants into DHI programs helps increasing benefits from the most suitable intervention. A major challenge with the roll-out and implementation of DHI, is in assigning participants into different interventions. The use of biopsychosocial model [18] for this purpose is not wide spread, due to limited personalized interventions formed on evidence-based data-driven models. Machine learning has changed the way data extraction and interpretation works by involving automatic sets of generic methods that have replaced the traditional statistical techniques. In this paper, we propose to investigate relevance of machine learning for this purpose and is carried out by studying different non-linear classifiers and compare their prediction accuracy to evaluate their suitability. Further, as a novel contribution, real-life biopsychosocial features are used as input in this study. The results help in developing an appropriate predictive classication model to assign participants into the most suitable DHI. We analyze biopsychosocial data generated from a DHI program and study their feature characteristics using scatter plots. While scatter plots are unable to reveal the linear relationships in the data-set, the use of classifiers can successfully identify which features are suitable predictors of mental ill health.
Adoption of blockchain technology : exploring the factors affecting organizational decision
- Malik, Saleem, Chadhar, Mehmood, Chetty, Madhu, Vatanasakdakul, Savanid
- Authors: Malik, Saleem , Chadhar, Mehmood , Chetty, Madhu , Vatanasakdakul, Savanid
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Human Behavior and Emerging Technologies Vol. 2022, no. (2022), p.
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- Description: Blockchain (BCT) is an emerging technology that promises many benefits for organizations, for instance, disintermediation, data security, data transparency, a single version of the truth, and trust among trading partners. Despite its multiple benefits, the adoption rate of BCT among organizations has not reached a significantly high level worldwide, thus requiring further research in this space. The present study addresses this issue in the Australian context. There is a knowledge gap in what specific factors, among the plethora of factors reported in the extant literature, affect the organizational adoption of BCT in Australia. To fill this gap, the study uses the qualitative interpretative research approach along with the technology-organization-environment (TOE) framework as a theoretical lens. The data was mainly drawn from the literature review and semi-structured interviews of the decision-makers and senior IT people from the BCT adopter and potential adopter organizations in Australia. According to the findings, perceived information transparency, perceived risks, organization innovativeness, organization learning capability, standards uncertainty, and competition intensity influence organizational adoption of BCT in Australia. These factors are exclusively identified in this study. The study also validates the influence of perceived benefits and perceived compatibility on BCT adoption that are reported in the past studies. Practically, these findings are helpful for the Australian government and public and private organizations to develop better policies and make informed decisions for the organizational adoption of BCT. The findings would guide decision-makers to think about the adoption of BCT strategically. The study also has theoretical implications explained in the discussion section. © 2022 Saleem Malik et al.
- Authors: Malik, Saleem , Chadhar, Mehmood , Chetty, Madhu , Vatanasakdakul, Savanid
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Human Behavior and Emerging Technologies Vol. 2022, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Blockchain (BCT) is an emerging technology that promises many benefits for organizations, for instance, disintermediation, data security, data transparency, a single version of the truth, and trust among trading partners. Despite its multiple benefits, the adoption rate of BCT among organizations has not reached a significantly high level worldwide, thus requiring further research in this space. The present study addresses this issue in the Australian context. There is a knowledge gap in what specific factors, among the plethora of factors reported in the extant literature, affect the organizational adoption of BCT in Australia. To fill this gap, the study uses the qualitative interpretative research approach along with the technology-organization-environment (TOE) framework as a theoretical lens. The data was mainly drawn from the literature review and semi-structured interviews of the decision-makers and senior IT people from the BCT adopter and potential adopter organizations in Australia. According to the findings, perceived information transparency, perceived risks, organization innovativeness, organization learning capability, standards uncertainty, and competition intensity influence organizational adoption of BCT in Australia. These factors are exclusively identified in this study. The study also validates the influence of perceived benefits and perceived compatibility on BCT adoption that are reported in the past studies. Practically, these findings are helpful for the Australian government and public and private organizations to develop better policies and make informed decisions for the organizational adoption of BCT. The findings would guide decision-makers to think about the adoption of BCT strategically. The study also has theoretical implications explained in the discussion section. © 2022 Saleem Malik et al.
Knowledge-based intelligent text simplification for biological relation extraction
- Gill, Jaskaran, Chetty, Madhu, Lim, Suryani, Hallinan, Jennifer
- Authors: Gill, Jaskaran , Chetty, Madhu , Lim, Suryani , Hallinan, Jennifer
- Date: 2023
- Type: Text , Journal article
- Relation: Informatics Vol. 10, no. 4 (2023), p.
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- Description: Relation extraction from biological publications plays a pivotal role in accelerating scientific discovery and advancing medical research. While vast amounts of this knowledge is stored within the published literature, extracting it manually from this continually growing volume of documents is becoming increasingly arduous. Recently, attention has been focused towards automatically extracting such knowledge using pre-trained Large Language Models (LLM) and deep-learning algorithms for automated relation extraction. However, the complex syntactic structure of biological sentences, with nested entities and domain-specific terminology, and insufficient annotated training corpora, poses major challenges in accurately capturing entity relationships from the unstructured data. To address these issues, in this paper, we propose a Knowledge-based Intelligent Text Simplification (KITS) approach focused on the accurate extraction of biological relations. KITS is able to precisely and accurately capture the relational context among various binary relations within the sentence, alongside preventing any potential changes in meaning for those sentences being simplified by KITS. The experiments show that the proposed technique, using well-known performance metrics, resulted in a 21% increase in precision, with only 25% of sentences simplified in the Learning Language in Logic (LLL) dataset. Combining the proposed method with BioBERT, the popular pre-trained LLM was able to outperform other state-of-the-art methods. © 2023 by the authors.
- Authors: Gill, Jaskaran , Chetty, Madhu , Lim, Suryani , Hallinan, Jennifer
- Date: 2023
- Type: Text , Journal article
- Relation: Informatics Vol. 10, no. 4 (2023), p.
- Full Text:
- Reviewed:
- Description: Relation extraction from biological publications plays a pivotal role in accelerating scientific discovery and advancing medical research. While vast amounts of this knowledge is stored within the published literature, extracting it manually from this continually growing volume of documents is becoming increasingly arduous. Recently, attention has been focused towards automatically extracting such knowledge using pre-trained Large Language Models (LLM) and deep-learning algorithms for automated relation extraction. However, the complex syntactic structure of biological sentences, with nested entities and domain-specific terminology, and insufficient annotated training corpora, poses major challenges in accurately capturing entity relationships from the unstructured data. To address these issues, in this paper, we propose a Knowledge-based Intelligent Text Simplification (KITS) approach focused on the accurate extraction of biological relations. KITS is able to precisely and accurately capture the relational context among various binary relations within the sentence, alongside preventing any potential changes in meaning for those sentences being simplified by KITS. The experiments show that the proposed technique, using well-known performance metrics, resulted in a 21% increase in precision, with only 25% of sentences simplified in the Learning Language in Logic (LLL) dataset. Combining the proposed method with BioBERT, the popular pre-trained LLM was able to outperform other state-of-the-art methods. © 2023 by the authors.
MICFuzzy : a maximal information content based fuzzy approach for reconstructing genetic networks
- Gamage, Hasini, Chetty, Madhu, Lim, Suryani, Hallinan, Jennifer
- Authors: Gamage, Hasini , Chetty, Madhu , Lim, Suryani , Hallinan, Jennifer
- Date: 2023
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 18, no. 7 July (2023), p.
- Full Text:
- Reviewed:
- Description: In systems biology, the accurate reconstruction of Gene Regulatory Networks (GRNs) is crucial since these networks can facilitate the solving of complex biological problems. Amongst the plethora of methods available for GRN reconstruction, information theory and fuzzy concepts-based methods have abiding popularity. However, most of these methods are not only complex, incurring a high computational burden, but they may also produce a high number of false positives, leading to inaccurate inferred networks. In this paper, we propose a novel hybrid fuzzy GRN inference model called MICFuzzy which involves the aggregation of the effects of Maximal Information Coefficient (MIC). This model has an information theory-based pre-processing stage, the output of which is applied as an input to the novel fuzzy model. In this preprocessing stage, the MIC component filters relevant genes for each target gene to significantly reduce the computational burden of the fuzzy model when selecting the regulatory genes from these filtered gene lists. The novel fuzzy model uses the regulatory effect of the identified activator-repressor gene pairs to determine target gene expression levels. This approach facilitates accurate network inference by generating a high number of true regulatory interactions while significantly reducing false regulatory predictions. The performance of MICFuzzy was evaluated using DREAM3 and DREAM4 challenge data, and the SOS real gene expression dataset. MICFuzzy outperformed the other state-of-the-art methods in terms of F-score, Matthews Correlation Coefficient, Structural Accuracy, and SS_mean, and outperformed most of them in terms of efficiency. MICFuzzy also had improved efficiency compared with the classical fuzzy model since the design of MICFuzzy leads to a reduction in combinatorial computation. Copyright: © 2023 Nakulugamuwa Gamage et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Authors: Gamage, Hasini , Chetty, Madhu , Lim, Suryani , Hallinan, Jennifer
- Date: 2023
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 18, no. 7 July (2023), p.
- Full Text:
- Reviewed:
- Description: In systems biology, the accurate reconstruction of Gene Regulatory Networks (GRNs) is crucial since these networks can facilitate the solving of complex biological problems. Amongst the plethora of methods available for GRN reconstruction, information theory and fuzzy concepts-based methods have abiding popularity. However, most of these methods are not only complex, incurring a high computational burden, but they may also produce a high number of false positives, leading to inaccurate inferred networks. In this paper, we propose a novel hybrid fuzzy GRN inference model called MICFuzzy which involves the aggregation of the effects of Maximal Information Coefficient (MIC). This model has an information theory-based pre-processing stage, the output of which is applied as an input to the novel fuzzy model. In this preprocessing stage, the MIC component filters relevant genes for each target gene to significantly reduce the computational burden of the fuzzy model when selecting the regulatory genes from these filtered gene lists. The novel fuzzy model uses the regulatory effect of the identified activator-repressor gene pairs to determine target gene expression levels. This approach facilitates accurate network inference by generating a high number of true regulatory interactions while significantly reducing false regulatory predictions. The performance of MICFuzzy was evaluated using DREAM3 and DREAM4 challenge data, and the SOS real gene expression dataset. MICFuzzy outperformed the other state-of-the-art methods in terms of F-score, Matthews Correlation Coefficient, Structural Accuracy, and SS_mean, and outperformed most of them in terms of efficiency. MICFuzzy also had improved efficiency compared with the classical fuzzy model since the design of MICFuzzy leads to a reduction in combinatorial computation. Copyright: © 2023 Nakulugamuwa Gamage et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Filter feature selection based boolean modelling for genetic network inference
- Gamage, Hasini, Chetty, Madhu, Shatte, Adrian, Hallinan, Jennifer
- Authors: Gamage, Hasini , Chetty, Madhu , Shatte, Adrian , Hallinan, Jennifer
- Date: 2022
- Type: Text , Journal article
- Relation: BioSystems Vol. 221, no. (2022), p.
- Full Text:
- Reviewed:
- Description: The reconstruction of Gene Regulatory Networks (GRNs) from time series gene expression data is highly relevant for the discovery of complex biological interactions and dynamics. Various computational strategies have been developed for this task, but most approaches have low computational efficiency and are not able to cope with high-dimensional, low sample-number, gene expression data. In this paper, we introduce a novel combined filter feature selection approach for efficient and accurate inference of GRNs. A Boolean framework for network modelling is used to demonstrate the efficacy of the proposed approach. Using discretized microarray expression data, the genes most relevant to each target gene are first filtered using ReliefF, an instance-based feature ranking method that is here applied for the first time to GRN inference. Then, further gene selection from the filtered-gene list is done using a mutual information-based min-redundancy max-relevance criterion by eliminating irrelevant genes. This combined method is executed on resampled datasets to finalize the optimal set of regulatory genes. Building upon our previous research, a Pearson correlation coefficient-based Boolean modelling approach is utilized for the efficient identification of the optimal regulatory rules associated with selected regulatory genes. The proposed approach was evaluated using gene expression datasets from small-scale and medium-scale real gene networks, and was observed to be more effective than Linear Discriminant Analysis, performed better than the individual feature selection methods, and obtained improved Structural Accuracy with a higher number of true positives than other state-of-the-art methods, while outperforming these methods with respect to Dynamic Accuracy and efficiency. © 2022 Elsevier B.V.
- Authors: Gamage, Hasini , Chetty, Madhu , Shatte, Adrian , Hallinan, Jennifer
- Date: 2022
- Type: Text , Journal article
- Relation: BioSystems Vol. 221, no. (2022), p.
- Full Text:
- Reviewed:
- Description: The reconstruction of Gene Regulatory Networks (GRNs) from time series gene expression data is highly relevant for the discovery of complex biological interactions and dynamics. Various computational strategies have been developed for this task, but most approaches have low computational efficiency and are not able to cope with high-dimensional, low sample-number, gene expression data. In this paper, we introduce a novel combined filter feature selection approach for efficient and accurate inference of GRNs. A Boolean framework for network modelling is used to demonstrate the efficacy of the proposed approach. Using discretized microarray expression data, the genes most relevant to each target gene are first filtered using ReliefF, an instance-based feature ranking method that is here applied for the first time to GRN inference. Then, further gene selection from the filtered-gene list is done using a mutual information-based min-redundancy max-relevance criterion by eliminating irrelevant genes. This combined method is executed on resampled datasets to finalize the optimal set of regulatory genes. Building upon our previous research, a Pearson correlation coefficient-based Boolean modelling approach is utilized for the efficient identification of the optimal regulatory rules associated with selected regulatory genes. The proposed approach was evaluated using gene expression datasets from small-scale and medium-scale real gene networks, and was observed to be more effective than Linear Discriminant Analysis, performed better than the individual feature selection methods, and obtained improved Structural Accuracy with a higher number of true positives than other state-of-the-art methods, while outperforming these methods with respect to Dynamic Accuracy and efficiency. © 2022 Elsevier B.V.
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