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ATHENA中的初始化参数扫描:在存在小主效应的情况下优化用于检测基因-基因相互作用的神经网络。

Initialization Parameter Sweep in ATHENA: Optimizing Neural Networks for Detecting Gene-Gene Interactions in the Presence of Small Main Effects.

作者信息

Holzinger Emily R, Buchanan Carrie C, Dudek Scott M, Torstenson Eric C, Turner Stephen D, Ritchie Marylyn D

机构信息

Ctr. for Human Genetics Research Dept. of Molecular Physiology & Biophysics; Vanderbilt University Nashville, TN 37232.

出版信息

Genet Evol Comput Conf. 2010;12:203-210. doi: 10.1145/1830483.1830519.

Abstract

Recent advances in genotyping technology have led to the generation of an enormous quantity of genetic data. Traditional methods of statistical analysis have proved insufficient in extracting all of the information about the genetic components of common, complex human diseases. A contributing factor to the problem of analysis is that amongst the small main effects of each single gene on disease susceptibility, there are non-linear, gene-gene interactions that can be difficult for traditional, parametric analyses to detect. In addition, exhaustively searching all multi-locus combinations has proved computationally impractical. Novel strategies for analysis have been developed to address these issues. The Analysis Tool for Heritable and Environmental Network Associations (ATHENA) is an analytical tool that incorporates grammatical evolution neural networks (GENN) to detect interactions among genetic factors. Initial parameters define how the evolutionary process will be implemented. This research addresses how different parameter settings affect detection of disease models involving interactions. In the current study, we iterate over multiple parameter values to determine which combinations appear optimal for detecting interactions in simulated data for multiple genetic models. Our results indicate that the factors that have the greatest influence on detection are: input variable encoding, population size, and parallel computation.

摘要

基因分型技术的最新进展已导致产生了大量的遗传数据。传统的统计分析方法已证明在提取有关常见复杂人类疾病遗传成分的所有信息方面是不够的。分析问题的一个促成因素是,在每个单基因对疾病易感性的微小主要影响中,存在非线性的基因-基因相互作用,传统的参数分析可能难以检测到这些相互作用。此外,详尽搜索所有多位点组合在计算上已证明是不切实际的。已开发出新颖的分析策略来解决这些问题。可遗传和环境网络关联分析工具(ATHENA)是一种分析工具,它结合了语法进化神经网络(GENN)来检测遗传因素之间的相互作用。初始参数定义了进化过程将如何实施。本研究探讨了不同的参数设置如何影响涉及相互作用的疾病模型的检测。在当前研究中,我们对多个参数值进行迭代,以确定哪些组合对于检测多个遗传模型的模拟数据中的相互作用似乎是最佳的。我们的结果表明,对检测影响最大的因素是:输入变量编码、群体大小和平行计算。

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