A new approach to detect epistasis utilizing parallel implementation of ant colony optimization by MapReduce framework

Genome-wide association studies (GWAS) involve the detection and interpretation of epistasis, which is responsible for the ‘missing heritability’ and influences common complex disease susceptibility. Many epistasis detection algorithms cannot be directly applied into GWAS as many combinations of genetic components are present in only a small amount of samples or even none at all. For a huge number of single nucleotide polymorphisms and inappropriate statistical tests, epistasis detection remains a computational and statistical challenge in genetic epidemiology. Here, we develop a novel method to identify epistatic interactions related to disease susceptibility utilizing an ant colony optimization strategy implemented by Google's MapReduce platform. We incorporate expert knowledge used to guide ants to make the best choice in the search process into the pheromone updating rule. We conduct sufficient experiments using simulated and real genome-wide data sets and experimental results demonstrate excellent performance of our algorithm compared with its competitors.     

对遗传算法困难度测量的基因关联法的研究

针对基因关联测度法的本质及意义进行了详细的理论剖析和实证研究.首先分析了反映遗传算法基因关联程度的标准化的基因关联方差与基因关联相关系数,进一步归纳出两个基本定理,并给予了严格的数学证明.最后用一些初等函数及NNK-模型对这一方法进行了实证分析,实验结果表明,对于困难问题该方法能够给予准确的判别,而对于某些较为容易的问题可能产生误判.     

The statistical mechanics of a polygenic character under stabilizing selection,mutation and drift

By exploiting an analogy between population genetics and statistical mechanics, we study the evolution of a polygenic trait under stabilizing selection, mutation and genetic drift. This requires us to track only four macroscopic variables, instead of the distribution of all the allele frequencies that influence the trait. These macroscopic variables are the expectations of: the trait mean and its square, the genetic variance, and of a measure of heterozygosity, and are derived from a generating function that is in turn derived by maximizing an entropy measure. These four macroscopics are enough to accurately describe the dynamics of the trait mean and of its genetic variance (and in principle of any other quantity). Unlike previous approaches that were based on an infinite series of moments or cumulants, which had to be truncated arbitrarily, our calculations provide a well-defined approximation procedure. We apply the framework to abrupt and gradual changes in the optimum, as well as to changes in the strength of stabilizing selection. Our approximations are surprisingly accurate, even for systems with as few as five loci. We find that when the effects of drift are included, the expected genetic variance is hardly altered by directional selection, even though it fluctuates in any particular instance. We also find hysteresis, showing that even after averaging over the microscopic variables, the macroscopic trajectories retain a memory of the underlying genetic states.