Linear modes of gene expression determined by independent component analysis

MOTIVATION: The expression of genes is controlled by specific combinations of cellular variables. We applied Independent Component Analysis (ICA) to gene expression data, deriving a linear model based on hidden variables, which we term 'expression modes'. The expression of each gene is a linear function of the expression modes, where, according to the ICA model, the linear influences of different modes show a minimal statistical dependence, and their distributions deviate sharply from the normal distribution. RESULTS: Studying cell cycle-related gene expression in yeast, we found that the dominant expression modes could be related to distinct biological functions, such as phases of the cell cycle or the mating response. Analysis of human lymphocytes revealed modes that were related to characteristic differences between cell types. With both data sets, the linear influences of the dominant modes showed distributions with large tails, indicating the existence of specifically up- and downregulated target genes. The expression modes and their influences can be used to visualize the samples and genes in low-dimensional spaces. A projection to expression modes helps to highlight particular biological functions, to reduce noise, and to compress the data in a biologically sensible way.