Mining for genotype-phenotype relations in Saccharomyces using partial least squares.
Mining for genotype-phenotype relations in Saccharomyces using partial least squares.
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DOI：
10.1186/1471-2105-12-318
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发表时间：
2011-08-03
影响因子：
3
通讯作者：
Snipen L
中科院分区：
文献类型：
--
作者：
Mehmood T;Martens H;Saebø S;Warringer J;Snipen L
多变量方法是重要的，因为它们的通用性和应用在许多领域，因为它提供了决定性的优势，在许多方面比单变量分析。全基因组关联研究正在迅速兴起，但现有方法对基因型和表型之间的多元关系关注较少。我们介绍了一种方法的基础上的BLAST方法提取信息的基因组序列和软保持偏最小二乘（ST-PLS）映射基因型-表型关系。将这种方法应用于模型酵母Saccharomyces cerevisiae的广泛数据集，我们发现基因型-表型之间的关系涉及令人惊讶的很少的基因，在这个意义上，绝大部分的表型变异可以用包含5791个基因的完整基因参考集的不到1%的变异来解释。这些表型影响基因的进化速度比非影响基因快20%，并且在细胞功能上分布不均匀，在细胞呼吸和转座等功能中具有强烈的富集。这些基因也富含已知的旁系同源物，终止密码子变异和拷贝数变异，这表明这种分子调整对酵母菌最近适应其生态位中的环境变化产生了不成比例的影响。基于BLAST和PLS的多变量方法得到的结果符合已知的酵母遗传学和基因本体论，从而验证了该方法提取了一组快速进化的基因，这些基因捕获了酵母菌株的遗传学。这种方法是值得追求的，未来的调查应作出改进的基因型信号的计算，以及变量选择过程中的PLS框架。
Multivariate approaches are important due to their versatility and applications in many fields as it provides decisive advantages over univariate analysis in many ways. Genome wide association studies are rapidly emerging, but approaches in hand pay less attention to multivariate relation between genotype and phenotype. We introduce a methodology based on a BLAST approach for extracting information from genomic sequences and Soft- Thresholding Partial Least Squares (ST-PLS) for mapping genotype-phenotype relations. Applying this methodology to an extensive data set for the model yeast Saccharomyces cerevisiae, we found that the relationship between genotype-phenotype involves surprisingly few genes in the sense that an overwhelmingly large fraction of the phenotypic variation can be explained by variation in less than 1% of the full gene reference set containing 5791 genes. These phenotype influencing genes were evolving 20% faster than non-influential genes and were unevenly distributed over cellular functions, with strong enrichments in functions such as cellular respiration and transposition. These genes were also enriched with known paralogs, stop codon variations and copy number variations, suggesting that such molecular adjustments have had a disproportionate influence on Saccharomyces yeasts recent adaptation to environmental changes in its ecological niche. BLAST and PLS based multivariate approach derived results that adhere to the known yeast phylogeny and gene ontology and thus verify that the methodology extracts a set of fast evolving genes that capture the phylogeny of the yeast strains. The approach is worth pursuing, and future investigations should be made to improve the computations of genotype signals as well as variable selection procedure within the PLS framework.
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