Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
PLoS Genet. 2011 Jan 20;7(1):e1001276. doi: 10.1371/journal.pgen.1001276.
Even within a defined cell type, the expression level of a gene differs in individual samples. The effects of genotype, measured factors such as environmental conditions, and their interactions have been explored in recent studies. Methods have also been developed to identify unmeasured intermediate factors that coherently influence transcript levels of multiple genes. Here, we show how to bring these two approaches together and analyse genetic effects in the context of inferred determinants of gene expression. We use a sparse factor analysis model to infer hidden factors, which we treat as intermediate cellular phenotypes that in turn affect gene expression in a yeast dataset. We find that the inferred phenotypes are associated with locus genotypes and environmental conditions and can explain genetic associations to genes in trans. For the first time, we consider and find interactions between genotype and intermediate phenotypes inferred from gene expression levels, complementing and extending established results.
即使在定义明确的细胞类型中，基因的表达水平在个体样本中也存在差异。最近的研究已经探讨了基因型、测量因素（如环境条件）及其相互作用的影响。还开发了方法来识别一致影响多个基因转录水平的未测量中间因素。在这里，我们展示了如何将这两种方法结合起来，并在推断的基因表达决定因素的背景下分析遗传效应。我们使用稀疏因子分析模型来推断隐藏因子，我们将这些因子视为中间细胞表型，这些表型反过来又会影响酵母数据集的基因表达。我们发现推断出的表型与基因座基因型和环境条件有关，并且可以解释基因之间的遗传关联。我们首次考虑并发现了从基因表达水平推断出的基因型和中间表型之间的相互作用，补充和扩展了已有的结果。
