Gene Knockout Identification Using an Extension of Bees Hill Flux Balance Analysis

Microbial strain optimisation for the overproduction of a desired phenotype has been a popular topic in recent years. Gene knockout is a genetic engineering technique that can modify the metabolism of microbial cells to obtain desirable phenotypes. Optimisation algorithms have been developed to identify the effects of gene knockout. However, the complexities of metabolic networks have made the process of identifying the effects of genetic modification on desirable phenotypes challenging. Furthermore, a vast number of reactions in cellular metabolism often lead to a combinatorial problem in obtaining optimal gene knockout. The computational time increases exponentially as the size of the problem increases. This work reports an extension of Bees Hill Flux Balance Analysis (BHFBA) to identify optimal gene knockouts to maximise the production yield of desired phenotypes while sustaining the growth rate. This proposed method functions by integrating OptKnock into BHFBA for validating the results automatically. The results show that the extension of BHFBA is suitable, reliable, and applicable in predicting gene knockout. Through several experiments conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as model organisms, extension of BHFBA has shown better performance in terms of computational time, stability, growth rate, and production yield of desired phenotypes

Gene Knockout Identification Using an Extension of Bees Hill Flux Balance Analysis

Microbial strain optimisation for the overproduction of a desired phenotype has been a popular topic in recent years. Gene knockout is a genetic engineering technique that can modify the metabolism of microbial cells to obtain desirable phenotypes. Optimisation algorithms have been developed to identify the effects of gene knockout. However, the complexities of metabolic networks have made the process of identifying the effects of genetic modification on desirable phenotypes challenging. Furthermore, a vast number of reactions in cellular metabolism often lead to a combinatorial problem in obtaining optimal gene knockout. The computational time increases exponentially as the size of the problem increases. This work reports an extension of Bees Hill Flux Balance Analysis (BHFBA) to identify optimal gene knockouts to maximise the production yield of desired phenotypes while sustaining the growth rate. This proposed method functions by integrating OptKnock into BHFBA for validating the results automatically. The results show that the extension of BHFBA is suitable, reliable, and applicable in predicting gene knockout. Through several experiments conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as model organisms, extension of BHFBA has shown better performance in terms of computational time, stability, growth rate, and production yield of desired phenotypes

Using bees hill flux balance analysis (BHFBA) for in silico microbial strain optimization

Microbial strains can be manipulated to improve product yield and improve growth characteristics. Optimization algorithms are developed to identify the effects of gene knockout on the results. However, this process is often faced the problem of being trapped in local minima and slow convergence due to repetitive iterations of algorithm. In this paper, we proposed Bees Hill Flux Balance Analysis (BHFBA) which is a hybrid of Bees Algorithm, Hill Climbing Algorithm and Flux Balance Analysis to solve the problems and improve the performance in predicting optimal sets of gene deletion for maximizing the growth rate and production yield of desired metabolite. Escherichia coli is the model organism in this paper. The list of knockout genes, growth rate and production yield after the deletion are the results from the experiments. BHFBA performed better in term of computational time, stability and production yield

Differential Bees Flux Balance Analysis with OptKnock for In Silico Microbial Strains Optimization

Microbial strains optimization for the overproduction of desired phenotype has been a popular topic in recent years. The strains can be optimized through several techniques in the field of genetic engineering. Gene knockout is a genetic engineering technique that can engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, the complexities of the metabolic networks have made the process to identify the effects of genetic modification on the desirable phenotypes challenging. Furthermore, a vast number of reactions in cellular metabolism often lead to the combinatorial problem in obtaining optimal gene deletion strategy. Basically, the size of a genome-scale metabolic model is usually large. As the size of the problem increases, the computation time increases exponentially. In this paper, we propose Differential Bees Flux Balance Analysis (DBFBA) with OptKnock to identify optimal gene knockout strategies for maximizing the production yield of desired phenotypes while sustaining the growth rate. This proposed method functions by improving the performance of a hybrid of Bees Algorithm and Flux Balance Analysis (BAFBA) by hybridizing Differential Evolution (DE) algorithm into neighborhood searching strategy of BAFBA. In addition, DBFBA is integrated with OptKnock to validate the results for improving the reliability the work. Through several experiments conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as the model organisms, DBFBA has shown a better performance in terms of computational time, stability, growth rate, and production yield of desired phenotypes compared to the methods used in previous works

Parameter estimation for simulation of glycolysis pathway by using an improved differential evolution

An improved differential evolution (DE) algorithm is proposed in this paper to optimize its performance in estimating the germane parameters for metabolic pathway data to simulate glycolysis pathway for Saccharomyces cerevisiae. This study presents an improved algorithm of parameter sensitivity test into the process of DE algorithm. The result of the improved algorithm is testifying to be supreme to the others estimation algorithms. The outcomes from this study promote estimating optimal kinetic parameters, shorter computation time and ameliorating the precision of simulated kinetic model for the experimental data

Identifying gene knockout strategies using a hybrid of bees algorithm and flux balance analysis for in silico optimization of microbial strains

Genome-scale metabolic networks reconstructions from different organisms have become popular in recent years. Genetic engineering is proven to be able to obtain the desirable phenotypes. Optimization algorithms are implemented in previous works to identify the effects of gene knockout on the results. However, the previous works face the problem of falling into local minima. Thus, a hybrid of Bees Algorithm and Flux Balance Analysis (BAFBA) is proposed in this paper to solve the local minima problem and to predict optimal sets of gene deletion for maximizing the growth rate of certain metabolite. This paper involves two case studies that consider the production of succinate and lactate as targets, by using E.coli as model organism. The results from this experiment are the list of knockout genes and the growth rate after the deletion. BAFBA shows better results compared to the other methods. The identified list suggests gene modifications over several pathways and may be useful in solving challenging genetic engineering problems

Using a dynamic bayesian network-based model for inference of escherichia coli SOS response pathway from gene expression data

Largely due to the technological advances in bioinformatics, researchers are now garnering interests in inferring gene regulatory networks (GRNs) from gene expression data which is otherwise unfeasible in the past. This is because of the need of researchers to uncover the potentially vast information and understand the dynamic behavior of the GRNs. In this regard, dynamic Bayesian network (DBN) has been broadly utilized for the inference of GRNs thanks to its ability to handle time-series microarray data and modeling feedback loops. Unfortunately, the commonly found missing values in gene expression data, and excessive computation time owing to the large search space whereby all genes are treated as potential regulators for a target gene, often impede the effectiveness of DBN in inferring GRNs. This paper proposes a DBN-based model with missing values imputation to improve inference efficiency, and potential regulators selection which intends to decrease computation time by selecting potential regulators based on expression changes. We tested our proposed model on the Escherichia coli SOS response pathway which is responsible for repairing damaged DNA of the bacterium. The experimental results showed reduced computation time and improved efficiency in detecting gene-gene relationship

Using an improved differential evolution algorithm for parameter estimation to simulate glycolysis pathway

This paper presents an improved Differential Evolution algorithm (IDE). It is aimed at improving its performance in estimating the relevant parameters for metabolic pathway data to simulate glycolysis pathway for yeast. Metabolic pathway data are expected to be of significant help in the development of efficient tools in kinetic modeling and parameter estimation platforms. Nonetheless, due to the noisy data and difficulty of the system in estimating myriad of parameters, many computation algorithms face obstacles and require longer computational time to estimate the relevant parameters. The IDE proposed in this paper is a hybrid of a Differential Evolution algorithm (DE) and a Kalman Filter (KF). The outcome of IDE is proven to be superior than a Genetic Algorithm (GA) and DE. The results of IDE from this experiment show estimated optimal kinetic parameters values, shorter computation time and better accuracy of simulated results compared to the other estimation algorithms

Gene Knockout Identification Using an Extension of Bees Hill Flux Balance Analysis

Microbial strain optimisation for the overproduction of a desired phenotype has been a popular topic in recent years. Gene knockout is a genetic engineering technique that can modify the metabolism of microbial cells to obtain desirable phenotypes. Optimisation algorithms have been developed to identify the effects of gene knockout. However, the complexities of metabolic networks have made the process of identifying the effects of genetic modification on desirable phenotypes challenging. Furthermore, a vast number of reactions in cellular metabolism often lead to a combinatorial problem in obtaining optimal gene knockout. The computational time increases exponentially as the size of the problem increases. This work reports an extension of Bees Hill Flux Balance Analysis (BHFBA) to identify optimal gene knockouts to maximise the production yield of desired phenotypes while sustaining the growth rate. This proposed method functions by integrating OptKnock into BHFBA for validating the results automatically. The results show that the extension of BHFBA is suitable, reliable, and applicable in predicting gene knockout. Through several experiments conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as model organisms, extension of BHFBA has shown better performance in terms of computational time, stability, growth rate, and production yield of desired phenotypes

Improved differential evolution algorithm for parameter estimation to improve the production of biochemical pathway

This paper introduces an improved Differential Evolution algorithm (IDE) which aims at improving its performance in estimating the relevant parameters for metabolic pathway data to simulate glycolysis pathway for yeast. Metabolic pathway data are expected to be of significant help in the development of efficient tools in kinetic modeling and parameter estimation platforms. Many computation algorithms face obstacles due to the noisy data and difficulty of the system in estimating myriad of parameters, and require longer computational time to estimate the relevant parameters. The proposed algorithm (IDE) in this paper is a hybrid of a Differential Evolution algorithm (DE) and a Kalman Filter (KF). The outcome of IDE is proven to be superior than Genetic Algorithm (GA) and DE. The results of IDE from experiments show estimated optimal kinetic parameters values, shorter computation time and increased accuracy for simulated results compared with other estimation algorithms