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Oliver Laule

Publications and source records attributed to Oliver Laule.

3 recordsLinked to original sources

Web-based analysis of the mouse transcriptome using Genevestigator.

BACKGROUND: Gene function analysis often requires a complex and laborious sequence of laboratory and computer-based experiments. Choosing an effective experimental design generally results from hypotheses derived from prior knowledge or experimentation. Knowledge obtained from meta-analyzing compendia of expression data with annotation libraries can provide significant clues in understanding gene and network function, resulting in better hypotheses that can be tested in the laboratory. DESCRIPTION: Genevestigator is a microarray database and analysis system allowing context-driven queries. Simple but powerful tools allow biologists with little computational background to retrieve information about when, where and how genes are expressed. We manually curated and quality-controlled 3110 mouse Affymetrix arrays from public repositories. Data queries can be run against an annotation library comprising 160 anatomy categories, 12 developmental stage groups, 80 stimuli, and 182 genetic backgrounds or modifications. The quality of results obtained through Genevestigator is illustrated by a number of biological scenarios that are substantiated by other types of experimentation in the literature. CONCLUSION: The Genevestigator-Mouse database effectively provides biologically meaningful results and can be accessed at https://www.genevestigator.ethz.ch.

Animals↗

Sparse graphical Gaussian modeling of the isoprenoid gene network in Arabidopsis thaliana.

We present a novel graphical Gaussian modeling approach for reverse engineering of genetic regulatory networks with many genes and few observations. When applying our approach to infer a gene network for isoprenoid biosynthesis in Arabidopsis thaliana, we detect modules of closely connected genes and candidate genes for possible cross-talk between the isoprenoid pathways. Genes of downstream pathways also fit well into the network. We evaluate our approach in a simulation study and using the yeast galactose network.

Arabidopsis↗

Crosstalk between cytosolic and plastidial pathways of isoprenoid biosynthesis in Arabidopsis thaliana.

In plants, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, the central intermediates in the biosynthesis of isoprenoids, is compartmentalized: the mevalonate (MVA) pathway, which is localized to the cytosol, is responsible for the synthesis of sterols, certain sesquiterpenes, and the side chain of ubiquinone; in contrast, the recently discovered MVA-independent pathway, which operates in plastids, is involved in providing the precursors for monoterpenes, certain sesquiterpenes, diterpenes, carotenoids, and the side chains of chlorophylls and plastoquinone. Specific inhibitors of the MVA pathway (lovastatin) and the MVA-independent pathway (fosmidomycin) were used to perturb biosynthetic flux in Arabidopsis thaliana seedlings. The interaction between both pathways was studied at the transcriptional level by using GeneChip (Affymetrix) microarrays and at the metabolite level by assaying chlorophylls, carotenoids, and sterols. Treatment of seedlings with lovastatin resulted in a transient decrease in sterol levels and a transient increase in carotenoid as well as chlorophyll levels. After the initial drop, sterol amounts in lovastatin-treated seedlings recovered to levels above controls. As a response to fosmidomycin treatment, a transient increase in sterol levels was observed, whereas chlorophyll and carotenoid amounts decreased dramatically when compared with controls. At 96 h after fosmidomycin addition, the levels of all metabolites assayed (sterols, chlorophylls, and carotenoids) were substantially lower than in controls. Interestingly, these inhibitor-mediated changes were not reflected in altered gene expression levels of the genes involved in sterol, chlorophyll, and carotenoid metabolism. The lack of correlation between gene expression patterns and the accumulation of isoprenoid metabolites indicates that posttranscriptional processes may play an important role in regulating flux through isoprenoid metabolic pathways.

Arabidopsis↗