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Biomedical subjects

Alvis Brazma

Publications and source records attributed to Alvis Brazma.

11 recordsLinked to original sources

Towards reconstruction of gene networks from expression data by supervised learning.

BACKGROUND: Microarray experiments are generating datasets that can help in reconstructing gene networks. One of the most important problems in network reconstruction is finding, for each gene in the network, which genes can affect it and how. We use a supervised learning approach to address this question by building decision-tree-related classifiers, which predict gene expression from the expression data of other genes. RESULTS: We present algorithms that work for continuous expression levels and do not require a priori discretization. We apply our method to publicly available data for the budding yeast cell cycle. The obtained classifiers can be presented as simple rules defining gene interrelations. In most cases the extracted rules confirm the existing knowledge about cell-cycle gene expression, while hitherto unknown relationships can be treated as new hypotheses. CONCLUSIONS: All the relations between the considered genes are consistent with the facts reported in the literature. This indicates that the approach presented here is valid and that the resulting rules can be used as elements for building and explaining gene networks.

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The European Bioinformatics Institute's data resources.

As the amount of biological data grows, so does the need for biologists to store and access this information in central repositories in a free and unambiguous manner. The European Bioinformatics Institute (EBI) hosts six core databases, which store information on DNA sequences (EMBL-Bank), protein sequences (SWISS-PROT and TrEMBL), protein structure (MSD), whole genomes (Ensembl) and gene expression (ArrayExpress). But just as a cell would be useless if it couldn't transcribe DNA or translate RNA, our resources would be compromised if each existed in isolation. We have therefore developed a range of tools that not only facilitate the deposition and retrieval of biological information, but also allow users to carry out searches that reflect the interconnectedness of biological information. The EBI's databases and tools are all available on our website at www.ebi.ac.uk.

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ArrayExpress--a public repository for microarray gene expression data at the EBI.

ArrayExpress is a new public database of microarray gene expression data at the EBI, which is a generic gene expression database designed to hold data from all microarray platforms. ArrayExpress uses the annotation standard Minimum Information About a Microarray Experiment (MIAME) and the associated XML data exchange format Microarray Gene Expression Markup Language (MAGE-ML) and it is designed to store well annotated data in a structured way. The ArrayExpress infrastructure consists of the database itself, data submissions in MAGE-ML format or via an online submission tool MIAMExpress, online database query interface, and the Expression Profiler online analysis tool. ArrayExpress accepts three types of submission, arrays, experiments and protocols, each of these is assigned an accession number. Help on data submission and annotation is provided by the curation team. The database can be queried on parameters such as author, laboratory, organism, experiment or array types. With an increasing number of organisations adopting MAGE-ML standard, the volume of submissions to ArrayExpress is increasing rapidly. The database can be accessed at http://www.ebi.ac.uk/arrayexpress.

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Global transcriptional responses of fission yeast to environmental stress.

We explored transcriptional responses of the fission yeast Schizosaccharomyces pombe to various environmental stresses. DNA microarrays were used to characterize changes in expression profiles of all known and predicted genes in response to five stress conditions: oxidative stress caused by hydrogen peroxide, heavy metal stress caused by cadmium, heat shock caused by temperature increase to 39 degrees C, osmotic stress caused by sorbitol, and DNA damage caused by the alkylating agent methylmethane sulfonate. We define a core environmental stress response (CESR) common to all, or most, stresses. There was a substantial overlap between CESR genes of fission yeast and the genes of budding yeast that are stereotypically regulated during stress. CESR genes were controlled primarily by the stress-activated mitogen-activated protein kinase Sty1p and the transcription factor Atf1p. S. pombe also activated gene expression programs more specialized for a given stress or a subset of stresses. In general, these "stress-specific" responses were less dependent on the Sty1p mitogen-activated protein kinase pathway and may involve specific regulatory factors. Promoter motifs associated with some of the groups of coregulated genes were identified. We compare and contrast global regulation of stress genes in fission and budding yeasts and discuss evolutionary implications.

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Design and implementation of microarray gene expression markup language (MAGE-ML).

BACKGROUND: Meaningful exchange of microarray data is currently difficult because it is rare that published data provide sufficient information depth or are even in the same format from one publication to another. Only when data can be easily exchanged will the entire biological community be able to derive the full benefit from such microarray studies. RESULTS: To this end we have developed three key ingredients towards standardizing the storage and exchange of microarray data. First, we have created a minimal information for the annotation of a microarray experiment (MIAME)-compliant conceptualization of microarray experiments modeled using the unified modeling language (UML) named MAGE-OM (microarray gene expression object model). Second, we have translated MAGE-OM into an XML-based data format, MAGE-ML, to facilitate the exchange of data. Third, some of us are now using MAGE (or its progenitors) in data production settings. Finally, we have developed a freely available software tool kit (MAGE-STK) that eases the integration of MAGE-ML into end users' systems. CONCLUSIONS: MAGE will help microarray data producers and users to exchange information by providing a common platform for data exchange, and MAGE-STK will make the adoption of MAGE easier.

Computer Simulation↗

Microarray data representation, annotation and storage.

Management and analysis of the huge amounts of data produced by microarray experiments is becoming one of the major bottlenecks in the utilization of this high-throughput technology. We describe the basic design of a microarray gene expression database to help microarray users and their informatics teams to set up their information services. We describe two data models--a simpler one called ArrayExpressB and the complete model ArrayExpressC, and discuss some implementation issues. For latest developments see http: wwwebi.ac.uk/arrayexpress

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Protein interaction verification and functional annotation by integrated analysis of genome-scale data.

Assays capable of determining the properties of thousands of genes in parallel present challenges with regard to accurate data processing and functional annotation. Collections of microarray expression data are applied here to assess the quality of different high-throughput protein interaction data sets. Significant differences are found. Confidence in 973 out of 5342 putative two-hybrid interactions from S. cerevisiae is increased. Besides verification, integration of expression and interaction data is employed to provide functional annotation for over 300 previously uncharacterized genes. The robustness of these approaches is demonstrated by experiments that test the in silico predictions made. This study shows how integration improves the utility of different types of functional genomic data and how well this contributes to functional annotation.

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Correlating gene promoters and expression in gene disruption experiments.

MOTIVATION: Finding putative transcription factor binding sites in the upstream sequences of similarly expressed genes has recently become a subject of intensive studies. In this paper we investigate how much gene expression regulation can be attributed to the presence of various binding sites in the gene promoters by correlating the binding sites and the changes in gene expression resulting from gene disruptions (e.g. knockouts). RESULTS: We have developed a data analysis method for comparing mRNA measurements of gene disruption experiments with information about gene promoters. The method was applied to a well-known dataset to uncover correlations between known transcription factor binding site motifs in the upstream regions of all S. cerevisiae genes and the gene expression changes in various gene disruption experiments. The possible explanations of the correlations were categorized and analyzed using e.g. expression cascades. Several correlations turned out to be consistent with existing biological knowledge while some new ones suggest themselves for further study. AVAILABILITY: The resulting tables are available at http://www.cs.helsinki.fi/u/kpalin/CorrDisrupt/.

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