Trichostatin A (TSA) is a histone deacetylase inhibitor that has antiproliferative and differentiation-inducing effects on cancer cells, and in cultures of primary hepatocytes has been shown to ...maintain xenobiotic metabolic capacity. Using an NMR-based metabolic profiling approach, we evaluated if the endogenous metabolome was stabilized and the normal metabolic phenotype retained in this model. Aqueous soluble metabolites were extracted from isolated rat hepatocytes after 44 and 92 h exposure to TSA (25 μM) together with time-matched controls and measured by 1H NMR spectroscopy. Multivariate analysis showed a clear difference in the global metabolic profile over time in control samples, while the TSA treated group was more closely clustered at both time points, suggesting that treatment reduced the time related effect on metabolism that was observed in the control. TSA treatment was associated with decreases in glycerophosphocholine, 3-hydroxybutyric acid, glycine and adenosine, an increase in glycogen, and a reduction in the decrease of inosine, hypoxanthine, and glutathione over time. Collectively, our data suggest that TSA treatment reduces the loss of a normal metabolic phenotype in cultured primary hepatocytes, improving the model as a tool to study endogenous liver metabolism, xenobiotic metabolism, and potentially affecting the accuracy of all biological assays in this system.
Principal Component Analysis (PCA) and other multi-variate models are often used in the analysis of "omics" data. These models contain much information which is currently neither easily accessible ...nor interpretable. Here we present an algorithmic method which has been developed to integrate this information with existing databases of background knowledge, stored in the form of known sets (for instance genesets or pathways). To make this accessible we have produced a Graphical User Interface (GUI) in Matlab which allows the overlay of known set information onto the loadings plot and thus improves the interpretability of the multi-variate model. For each known set the optimal convex hull, covering a subset of elements from the known set, is found through a search algorithm and displayed. In this paper we discuss two main topics; the details of the search algorithm for the optimal convex hull for this problem and the GUI interface which is freely available for download for academic use.
This paper presents important new findings for a new method for evolving individual programs with multiple chromosomes. Previous results have shown that evolving individuals with multiple chromosomes ...produced improved results over evolving individuals with a single chromosome. The multiple chromosomes are organised along two axes; there are a number of different chromosomes and a number of copies of each chromosome. This paper investigates the effects which these two axes have on the performance of the algorithm; whether the improvement in performance comes from just one of these features or whether it is a combination of them both
Embedded Cartesian Genetic Programming (ECGP) is an extension of Cartesian Genetic Programming (CGP) that can automatically acquire, evolve and re-use partial solutions in the form of modules. In ...this paper, we introduce for the first time a new multi-chromosome approach to CGP and ECGP that allows difficult problems with multiple outputs to be broken down into many smaller, simpler problems with single outputs, whilst still encoding the entire solution in a single genotype. We also propose a multi-chromosome evolutionary strategy which selects the best chromosomes from the entire population to form the new fittest individual, which may not have been present in the population. The multi-chromosome approach to CGP and ECGP is tested on a number of multiple output digital circuits. Computational Effort figures are calculated for each problem and compared against those for CGP and ECGP. The results indicate that the use of multiple chromosomes in both CGP and ECGP provide a significant performance increase on all problems tested.
Multi-chromosomal genetic programming Cavill, Rachel; Smith, Steve; Tyrrell, Andy
Genetic And Evolutionary Computation Conference: Proceedings of the 2005 conference on Genetic and evolutionary computation; 25-29 June 2005,
06/2005
Conference Proceeding
Odprti dostop
This paper introduces an evolutionary algorithm which uses multiple chromosomes to evolve solutions to a symbolic regression problem. Inspiration for this algorithm is provided by the existence of ...multiple chromosomes in natural evolution, particularly in plants. A multi-chromosomal system usually requires a dominance system and subsequently dominance in nature and in previous artificial evolutionary systems has also been considered. An implementation of a multi-chromosomal system is presented with initial results which support the use of multi-chromosomal techniques in evolutionary algorithms.
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