Evolutionary algorithms in dynamic environments

The file attached to this record is the author's final peer reviewed version.Evolutionary algorithms (EAs) are widely and often used for solving stationary optimization problems where the fitness landscape or objective function does not change during the course of computation. However, the environments of real world optimization problems may fluctuate or change sharply. If the optimization problem is dynamic, the goal is no longer to find the extrema, but to track their progression through the search space as closely as possible. All kinds of approaches that have been proposed to make EAs suitable for the dynamic environments are surveyed, such as increasing diversity, maintaining diversity, memory based approaches, multi-population approaches and so on

Fast Genome-Wide QTL Association Mapping on Pedigree and Population Data

Since most analysis software for genome-wide association studies (GWAS) currently exploit only unrelated individuals, there is a need for efficient applications that can handle general pedigree data or mixtures of both population and pedigree data. Even data sets thought to consist of only unrelated individuals may include cryptic relationships that can lead to false positives if not discovered and controlled for. In addition, family designs possess compelling advantages. They are better equipped to detect rare variants, control for population stratification, and facilitate the study of parent-of-origin effects. Pedigrees selected for extreme trait values often segregate a single gene with strong effect. Finally, many pedigrees are available as an important legacy from the era of linkage analysis. Unfortunately, pedigree likelihoods are notoriously hard to compute. In this paper we re-examine the computational bottlenecks and implement ultra-fast pedigree-based GWAS analysis. Kinship coefficients can either be based on explicitly provided pedigrees or automatically estimated from dense markers. Our strategy (a) works for random sample data, pedigree data, or a mix of both; (b) entails no loss of power; (c) allows for any number of covariate adjustments, including correction for population stratification; (d) allows for testing SNPs under additive, dominant, and recessive models; and (e) accommodates both univariate and multivariate quantitative traits. On a typical personal computer (6 CPU cores at 2.67 GHz), analyzing a univariate HDL (high-density lipoprotein) trait from the San Antonio Family Heart Study (935,392 SNPs on 1357 individuals in 124 pedigrees) takes less than 2 minutes and 1.5 GB of memory. Complete multivariate QTL analysis of the three time-points of the longitudinal HDL multivariate trait takes less than 5 minutes and 1.5 GB of memory

Beyond Biomass: Valuing Genetic Diversity in Natural Resource Management

Strategies for increasing production of goods from working and natural systems have raised concerns that the diversity of species on which these services depend may be eroding. This loss of natural capital threatens to homogenize global food supplies and compromise the stability of human welfare. We assess the trade off between artificial augmentation of biomass and degradation of biodiversity underlying a populations' ability to adapt to shocks. Our application involves the augmentation of wild stocks of salmon. Practices in this system have generated warnings that genetic erosion may lead to a loss of the “portfolio effect” and the value of this loss is not accounted for in decision making. We construct an integrated bioeconomic model of salmon biomass and genetic diversity. Our results show how practices that homogenize natural systems can still generate positive returns. However, the substitution of more physical capital and labor for natural capital must be maintained for gains to persist, weakens the capacity for adaptation should this investment cease, and can cause substantial loss of population wildness. We apply an emerging optimization method—approximate dynamic programming—to solve the model without simplifying restrictions imposed previously

COMPARISON OF METHODS INCORPORATING COVARIATES INTO AFFECTED SIB PAIR LINKAGE ANALYSIS

Complex diseases such as type 2 diabetes, hypertension and psychiatric disorders have been major public health problems in US. In order to increase the power in the linkage analysis of complex traits, genetic heterogeneity has to be taken into account. During the past few years, several methods have been proposed for dealing with this issue by incorporating covariate information into the affected sib pair (ASP) analysis. However, it is still not clear how these approaches perform under different gene-environment (G x E) interactions. The covariate statistics evaluated in this study are: (1) mixture model; (2) general conditional-logistic model (LODPAL); (3) multinomial logistic regression models (MLRM under no dominance, no additive and min-max restriction); (4) extension of the maximum-likelihood-binomial approach (MLB); (5) ordered-subset analysis (OSA with three different rank orders: high-to-low, low-to-high and optimal-slice); (6) logistic regression modeling (COVLINK). Based on the chromosome-based approach, we have written simulation programs to generate data under various G x E models and disease models. We first define the empirical statistical significance thresholds using C2, the environmental risk factor, under the null hypothesis. We then evaluate the power of the covariate statistics when different covariates are used. We also compare the performance of the covariate statistics with the model-free methods (Sall and Spair). In all three G x E interaction models, most covariate methods perform better when using C1, the covariate with G x E interaction effect, than when using C2 or the random noise covariate C3, except for MLB and the low-to-high OSA method. Comparing with the model-free methods (using Sall as the baseline), mixture model and the high-to-low OSA method perform the best of the covariate statistics when using C1. However, when using C2 or C3, most covariate statistics provide less power than Sall. Only MLB has comparable power to Sall across all genetic models. According to our results, in different G x E interactions, one should apply the appropriate covariate statistic and include the suitable type of covariates carefully

Genetic Basis of Thermal Divergence in Saccharomyces species

The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is relatively heat tolerant, whereas S. uvarum is heat sensitive but outperforms S. cerevisiae at 4 degree C. Gene expression analysis with an S. cerevisiae and S. uvarum hybrid revealed a small set of 136 genes with temperature-dependent cis-acting differences, suggesting that the temperature divergence has not caused widespread cis-regulatory divergence. Using a genome-wide non-complementation screen, I found a single nuclear-encoded gene with a modest contribution to heat tolerance, and a large effect of the species\u27 mitochondrial DNA (mitotype). Recombinant mitotypes and allele replacements indicate multiple mitochondria-encoded genes contribute to thermal divergence, with the coding sequence of COX1 showing a moderate effect on both heat and cold tolerance. The non-complementation approach also identified allele differences of CUP2, a copper-binding transcription factor, in copper resistance of S. cerevisiae and S. uvarum. Chimeric alleles showed that multiple changes underlie the resistance of S. cerevisiae CUP2, with cis-regulatory changes having a larger effect than coding changes. Taken together, my findings suggest that evolution of interspecific phenotypic differences often involves accumulation of small-to-medium effect changes, such as those in mitochondrial DNA and CUP2, and can occur through both coding and cis-regulatory changes

Data analysis methods for copy number discovery and interpretation

Copy number variation (CNV) is an important type of genetic variation that can give rise to a wide variety of phenotypic traits. Differences in copy number are thought to play major roles in processes that involve dosage sensitive genes, providing beneficial, deleterious or neutral modifications to individual phenotypes. Copy number analysis has long been a standard in clinical cytogenetic laboratories. Gene deletions and duplications can often be linked with genetic Syndromes such as: the 7q11.23 deletion of Williams-­‐Bueren Syndrome, the 22q11 deletion of DiGeorge syndrome and the 17q11.2 duplication of Potocki-­‐Lupski syndrome. Interestingly, copy number based genomic disorders often display reciprocal deletion / duplication syndromes, with the latter frequently exhibiting milder symptoms. Moreover, the study of chromosomal imbalances plays a key role in cancer research. The datasets used for the development of analysis methods during this project are generated as part of the cutting-­‐edge translational project, Deciphering Developmental Disorders (DDD). This project, the DDD, is the first of its kind and will directly apply state of the art technologies, in the form of ultra-­‐high resolution microarray and next generation sequencing (NGS), to real-­‐time genetic clinical practice. It is collaboration between the Wellcome Trust Sanger Institute (WTSI) and the National Health Service (NHS) involving the 24 regional genetic services across the UK and Ireland. Although the application of DNA microarrays for the detection of CNVs is well established, individual change point detection algorithms often display variable performances. The definition of an optimal set of parameters for achieving a certain level of performance is rarely straightforward, especially where data qualities vary ... [cont.]