On Genetic Programming and Knowledge Discovery in Transcriptome

Rowland, J. J. (2004) On Genetic Programming and Knowledge Discovery in Transcriptome Data. Proc. IEEE Congress on Evolutionary Computation, Portland, Oregon. pp 158-165. ISBN 0-7803-8515-2

Adaptive denoising in spectral analysis by genetic programming

Rowland, J.J. and Taylor, J. (2002). Adaptive denoising in spectral analysis by genetic programming. Proc. IEEE Congress on Evolutionary Computation (part of WCCI), May 2002. pp 133-138. ISBN 0-7803-7281-6

Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease

McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs).We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients.Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies.We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.

Soil differentiation using fingerprint Fourier transform infrared spectroscopy, chemometrics and genetic algorithm-based feature selection

Elliott, G. N., Worgan, H., Broadhurst, D. I., Draper, J. H., Scullion, J. (2007). Soil differentiation using fingerprint Fourier transform infrared spectroscopy, chemometrics and genetic algorithm-based feature selection. Soil Biology & Biochemistry, 39 (11), 2888-2896. Sponsorship: BBSRC / NERC RAE2008

A genetic algorithm based economic dispatch (GAED) with environmental constraint optimisation

The role of renewable energy in power systems is becoming more significant due to the increasing cost of fossil fuels and climate change concerns. However, the inclusion of Renewable Energy Generators (REG), such as wind power, has created additional problems for power system operators due to the variability and lower predictability of output of most REGs, with the Economic Dispatch (ED) problem being particularly difficult to resolve. In previous papers we had reported on the inclusion of wind power in the ED calculations. The simulation had been performed using a system model with wind power as an intermittent source, and the results of the simulation have been compared to that of the Direct Search Method (DSM) for similar cases. In this paper we report on our continuing investigations into using Genetic Algorithms (GA) for ED for an independent power system with a significant amount of wind energy in its generator portfolio. The results demonstrate, in line with previous reports in the literature, the effectiveness of GA when measured against a benchmark technique such as DSM.

Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS:We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate [greater than or equal to]80%, minor allele frequency [greater than or equal to]10%, Hardy-Weinberg test p [greater than or equal to] 0.001).RESULTS:In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. CONCLUSION: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.

Exponential sensitivity of noise-driven switching in genetic networks

Cells are known to utilize biochemical noise to probabilistically switch between distinct gene expression states. We demonstrate that such noise-driven switching is dominated by tails of probability distributions and is therefore exponentially sensitive to changes in physiological parameters such as transcription and translation rates. However, provided mRNA lifetimes are short, switching can still be accurately simulated using protein-only models of gene expression. Exponential sensitivity limits the robustness of noise-driven switching, suggesting cells may use other mechanisms in order to switch reliably.

How Good are Genetic Algorithms at Finding Large Cliques: An Experimental Study

This paper investigates the power of genetic algorithms at solving the MAX-CLIQUE problem. We measure the performance of a standard genetic algorithm on an elementary set of problem instances consisting of embedded cliques in random graphs. We indicate the need for improvement, and introduce a new genetic algorithm, the multi-phase annealed GA, which exhibits superior performance on the same problem set. As we scale up the problem size and test on \hard" benchmark instances, we notice a degraded performance in the algorithm caused by premature convergence to local minima. To alleviate this problem, a sequence of modi cations are implemented ranging from changes in input representation to systematic local search. The most recent version, called union GA, incorporates the features of union cross-over, greedy replacement, and diversity enhancement. It shows a marked speed-up in the number of iterations required to find a given solution, as well as some improvement in the clique size found. We discuss issues related to the SIMD implementation of the genetic algorithms on a Thinking Machines CM-5, which was necessitated by the intrinsically high time complexity (O(n3)) of the serial algorithm for computing one iteration. Our preliminary conclusions are: (1) a genetic algorithm needs to be heavily customized to work "well" for the clique problem; (2) a GA is computationally very expensive, and its use is only recommended if it is known to find larger cliques than other algorithms; (3) although our customization e ort is bringing forth continued improvements, there is no clear evidence, at this time, that a GA will have better success in circumventing local minima.

A Lower-Bound Result on the Power of a Genetic Algorithm

This paper presents a lower-bound result on the computational power of a genetic algorithm in the context of combinatorial optimization. We describe a new genetic algorithm, the merged genetic algorithm, and prove that for the class of monotonic functions, the algorithm finds the optimal solution, and does so with an exponential convergence rate. The analysis pertains to the ideal behavior of the algorithm where the main task reduces to showing convergence of probability distributions over the search space of combinatorial structures to the optimal one. We take exponential convergence to be indicative of efficient solvability for the sample-bounded algorithm, although a sampling theory is needed to better relate the limit behavior to actual behavior. The paper concludes with a discussion of some immediate problems that lie ahead.