School of Mathematics and Statistics - Research Publications

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Author: Oshlack, Alicia × Author: Smyth, Gordon × End date: 2009 × Start date: 2007 ×

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    Normalization of boutique two-color microarrays with a high proportion of differentially expressed probes
    Oshlack, A ; Emslie, D ; Corcoran, LM ; Smyth, GK (BMC, 2007)
    Normalization is critical for removing systematic variation from microarray data. For two-color microarray platforms, intensity-dependent lowess normalization is commonly used to correct relative gene expression values for biases. Here we outline a normalization method for use when the assumptions of lowess normalization fail. Specifically, this can occur when specialized boutique arrays are constructed that contain a subset of genes selected to test particular biological functions.
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    Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures
    Blekhman, R ; Oshlack, A ; Chabot, AE ; Smyth, GK ; Gilad, Y ; McVean, G (PUBLIC LIBRARY SCIENCE, 2008-11)
    Regulatory changes have long been hypothesized to play an important role in primate evolution. To identify adaptive regulatory changes in humans, we performed a genome-wide survey for genes in which regulation has likely evolved under natural selection. To do so, we used a multi-species microarray to measure gene expression levels in livers, kidneys, and hearts from six humans, chimpanzees, and rhesus macaques. This comparative gene expression data allowed us to identify a large number of genes, as well as specific pathways, whose inter-species expression profiles are consistent with the action of stabilizing or directional selection on gene regulation. Among the latter set, we found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. In addition, we found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes in which regulation evolves under natural selection. These observations are consistent with the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level.