Hybrid of ant colony optimization and flux variability analysis for improving metabolites production

Metabolic engineering has been successfully used for the production of a variety of useful compounds such as L-phenylalanine and biohydrogen that received high demand on food, pharmaceutical, fossil fuels, and energy industries. Reaction deletion is one of the strategies of in silico metabolic engineering that can alter the metabolism of microbial cells with the objective to get the desired phenotypes. However, due to the size and complexity of metabolic networks, it is difficult to determine the near-optimal set of reactions to be knocked out. The complexity of the metabolic network is also caused by the presence of competing pathway that may interrupt the high production of a desireable metabolite. Consequently, this factor leads to low Biomass-Product Coupled Yield (BPCY), production rate and growth rate. Other than that, inefficiency of existing algorithms in modelling high growth rate and production rate is another problem that should be handled and solved. Therefore, this research proposed a hybrid algorithm comprising Ant Colony Optimization and Flux Variability Analysis (ACOFVA) to identify the best reaction combination to be knocked out to improve the production of desired metabolites in microorganisms. Based on the experimental results, ACOFVA shows an increase in terms of BPCY and production rate of L-Phenylalanine in Yeast and biohydrogen in Cyanobacteria, while maintaining the optimal growth rate for the target organism. Besides, suggested reactions to be knocked out for improving the production yield of L-Phenylalanine and biohydrogen have been identified and validated through the biological database. The algorithm also shows a good performance with better production rate and BPCY of L-Phenylalanine and biohydrogen than existing results

Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147855/1/gbb12502.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147855/2/gbb12502-sup-0002-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147855/3/gbb12502_am.pd

Co-expression gene networks and machine-learning algorithms unveil a core genetic toolkit for reproductive division of labour in rudimentary insect societies

The evolution of eusociality requires that individuals forgo some or all their own reproduction to assist the reproduction of others in their group, such as a primary egg-laying queen. A major open question is how genes and genetic pathways sculpt the evolution of eusociality, especially in rudimentary forms of sociality—those with smaller cooperative nests when compared with species such as honeybees that possess large societies. We lack comprehensive comparative studies examining shared patterns and processes across multiple social lineages. Here we examine the mechanisms of molecular convergence across two lineages of bees and wasps exhibiting such rudimentary societies. These societies consist of few individuals and their life histories range from facultative to obligately social. Using six species across four independent origins of sociality, we conduct a comparative meta-analysis of publicly available transcriptomes. Standard methods detected little similarity in patterns of differential gene expression in brain transcriptomes among reproductive and non-reproductive individuals across species. By contrast, both supervised machine learning and consensus co-expression network approaches uncovered sets of genes with conserved expression patterns among reproductive and non-reproductive phenotypes across species. These sets overlap substantially, and may comprise a shared genetic “toolkit” for sociality across the distantly related taxa of bees and wasps and independently evolved lineages of sociality. We also found many lineage-specific genes and co-expression modules associated with social phenotypes and possible signatures of shared life-history traits. These results reveal how taxon-specific molecular mechanisms complement a core toolkit of molecular processes in sculpting traits related to the evolution of eusociality

Neutral space analysis for a Boolean network model of the fission yeast cell cycle network

BackgroundInteractions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gene expression, such as the cell cycle, which can be analyzed through its GRN, where deregulation can lead to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast. An approach to study the robustness of GRN is through the neutral space. In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks that share the same state sequences of the fission yeast cell cycle.ResultsThrough simulations it was found that in the generated neutral graph, the functional networks that are not in the wildtype connected component have in general a Hamming distance more than 3 with the wildtype, and more than 10 between the other disconnected functional networks. Significant differences were found between the functional networks in the connected component of the wildtype network and the rest of the network, not only at a topological level, but also at the state space level, where significant differences in the distribution of the basin of attraction for the G1 fixed point was found for deterministic updating schemes.ConclusionsIn general, functional networks in the wildtype network connected component, can mutate up to no more than 3 times, then they reach a point of no return where the networks leave the connected component of the wildtype. The proposed method to construct a neutral graph is general and can be used to explore the neutral space of other biologically interesting networks, and also formulate new biological hypotheses studying the functional networks in the wildtype network connected component

Hybrid approach for metabolites production using differential evolution and minimization of metabolic adjustment

Microbial strains can be optimized using metabolic engineering which implements gene knockout techniques. These techniques manipulate potential genes to increase the yield of metabolites through restructuring metabolic networks. Nowadays, several hybrid optimization algorithms have been proposed to optimize the microbial strains. However, the existing algorithms were unable to obtain optimal strains because the nonessential genes are hardly to be diagnosed and need to be removed due to high complexity of metabolic network. Therefore, the main goal of this study is to overcome the limitation of the existing algorithms by proposing a hybrid of Differential Evolution and Minimization of Metabolic Adjustments (DEMOMA). Differential Evolution (DE) is known as population-based stochastic search algorithm with few tuneable parameter control. Minimization of Metabolic Adjustment (MOMA) is one of the constraint based algorithms which act to simulate the cellular metabolism after perturbation (gene knockout) occurred to the metabolic model. The strength of MOMA is the ability to simulate the strains that have undergone mutation precisely compared to Flux Balance Analysis. The data set used for the production of fumaric acid is S. cerevisiae whereas data set for lycopene production is Y. lipolytica metabolic networks model. Experimental results show that the DEMOMA was able to improve the growth rate for the fumaric acid production rate while for the lycopene production, Biomass Product Coupled Yield (BPCY) and production rate were both able to be optimized

Caste development and reproduction: a genome-wide analysis of hallmarks of insect eusociality

The honey bee queen and worker castes are a model system for developmental plasticity. We used established expressed sequence tag information for a Gene Ontology based annotation of genes that are differentially expressed during caste development. Metabolic regulation emerged as a major theme, with a caste-specific difference in the expression of oxidoreductases vs. hydrolases. Motif searches in upstream regions revealed group-specific motifs, providing an entry point to cis-regulatory network studies on caste genes. For genes putatively involved in reproduction, meiosis-associated factors came out as highly conserved, whereas some determinants of embryonic axes either do not have clear orthologs (bag of marbles, gurken, torso), or appear to be lacking (trunk) in the bee genome. Our results are the outcome of a first genome-based initiative to provide an annotated framework for trends in gene regulation during female caste differentiation (representing developmental plasticity) and reproduction

Molecular determinants of caste differentiation in the highly eusocial honeybee Apis mellifera

<p>Abstract</p> <p>Background</p> <p>In honeybees, differential feeding of female larvae promotes the occurrence of two different phenotypes, a queen and a worker, from identical genotypes, through incremental alterations, which affect general growth, and character state alterations that result in the presence or absence of specific structures. Although previous studies revealed a link between incremental alterations and differential expression of physiometabolic genes, the molecular changes accompanying character state alterations remain unknown.</p> <p>Results</p> <p>By using cDNA microarray analyses of >6,000 <it>Apis mellifera </it>ESTs, we found 240 differentially expressed genes (DEGs) between developing queens and workers. Many genes recorded as up-regulated in prospective workers appear to be unique to <it>A. mellifera</it>, suggesting that the workers' developmental pathway involves the participation of novel genes. Workers up-regulate more developmental genes than queens, whereas queens up-regulate a greater proportion of physiometabolic genes, including genes coding for metabolic enzymes and genes whose products are known to regulate the rate of mass-transforming processes and the general growth of the organism (e.g., <it>tor</it>). Many DEGs are likely to be involved in processes favoring the development of caste-biased structures, like brain, legs and ovaries, as well as genes that code for cytoskeleton constituents. Treatment of developing worker larvae with juvenile hormone (JH) revealed 52 JH responsive genes, specifically during the critical period of caste development. Using Gibbs sampling and Expectation Maximization algorithms, we discovered eight overrepresented <it>cis</it>-elements from four gene groups. Graph theory and complex networks concepts were adopted to attain powerful graphical representations of the interrelation between <it>cis</it>-elements and genes and objectively quantify the degree of relationship between these entities.</p> <p>Conclusion</p> <p>We suggest that clusters of functionally related DEGs are co-regulated during caste development in honeybees. This network of interactions is activated by nutrition-driven stimuli in early larval stages. Our data are consistent with the hypothesis that JH is a key component of the developmental determination of queen-like characters. Finally, we propose a conceptual model of caste differentiation in <it>A. mellifera </it>based on gene-regulatory networks.</p