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Biomedical subjects

Alvis Brazma

Publications and source records attributed to Alvis Brazma.

At least 19 recordsLinked to original sources

A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB.

BACKGROUND: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. RESULTS: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. CONCLUSION: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML.

Computational Biology↗

Modelling in molecular biology: describing transcription regulatory networks at different scales.

Approaches to describe gene regulation networks can be categorized by increasing detail, as network parts lists, network topology models, network control logic models or dynamic models. We discuss the current state of the art for each of these approaches. We study the relationship between different topology models, and give examples how they can be used to infer functional annotations for genes of unknown function. We introduce a new simple way of describing dynamic models called finite state linear model (FSLM). We discuss the gap between the parts list and topology models on one hand, and network logic and dynamic models, on the other hand. The first two classes of models have reached a genome-wide scale, while for the other model classes high-throughput technologies are yet to make a major impact.

Computational Biology↗

Data storage and analysis in ArrayExpress.

ArrayExpress is a public resource for microarray data that has two major goals: to serve as an archive providing access to microarray data supporting publications and to build a knowledge base of gene expression profiles. ArrayExpress consists of two tightly integrated databases: ArrayExpress repository, which is an archive, and ArrayExpress data warehouse, which contains reannotated data and is optimized for queries. As of December 2005, ArrayExpress contains gene expression and other microarray data from almost 35,000 hybridizations, comprising over 1200 studies, covering 70 different species. Most data are related to peer-reviewed publications. Password-protected access to prepublication data is provided for reviewers and authors. Data in the repository can be queried by various parameters such as species, authors, or words used in the experiment description. The data warehouse provides a wide range of queries, including ones based on gene and sample properties, and provides capabilities to retrieve data combined from different studies. The ArrayExpress resource also includes Expression Profiler (EP)-a microarray data mining, analysis, and visualization tool-and MIAMExpress-an online data submission tool. This chapter describes all major ArrayExpress components from the user perspective: how to submit to, retrieve from, and analyze data in ArrayExpress.

Animals↗

Standards for systems biology.

High-throughput technologies are generating large amounts of complex data that have to be stored in databases, communicated to various data analysis tools and interpreted by scientists. Data representation and communication standards are needed to implement these steps efficiently. Here we give a classification of various standards related to systems biology and discuss various aspects of standardization in life sciences in general. Why are some standards more successful than others, what are the prerequisites for a standard to succeed and what are the possible pitfalls?

Animals↗

MGED standards: work in progress.

The Microarray Gene Expression Data (MGED) society is an international organization established in 1999 for facilitating sharing of functional genomics and proteomics array data. To facilitate microarray data sharing, the MGED society has been working in establishing the relevant data standards. The three main components (which will be described in more detail later) of MGED standards are Minimum Information About a Microarray Experiment (MIAME), a document that outlines the minimum information that should be reported about a microarray experiment to enable its unambiguous interpretation and reproduction; MAGE, which consists of three parts, The Microarray Gene Expression Object Model (MAGE-OM), an XML-based document exchange format (MAGE-ML), which is derived directly from the object model, and the supporting tool kit MAGEstk; and MO, or MGED Ontology, which defines sets of common terms and annotation rules for microarray experiments, enabling unambiguous annotation and efficient queries, data analysis and data exchange without loss of meaning. We discuss here how these standards have been established, how they have evolved, and how they are used.

Animals↗

Development of the Minimum Information Specification for In Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE).

We describe the creation process of the Minimum Information Specification for In Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE). Modeled after the existing minimum information specification for microarray data, we created a new specification for gene expression localization experiments, initially to facilitate data sharing within a consortium. After successful use within the consortium, the specification was circulated to members of the wider biomedical research community for comment and refinement. After a period of acquiring many new suggested requirements, it was necessary to enter a final phase of excluding those requirements that were deemed inappropriate as a minimum requirement for all experiments. The full specification will soon be published as a version 1.0 proposal to the community, upon which a more full discussion must take place so that the final specification may be achieved with the involvement of the whole community.

Computational Biology↗

ChroCoLoc: an application for calculating the probability of co-localization of microarray gene expression.

UNLABELLED: With the production of whole genome microarray chips the ability arises to investigate whether the regulation of particular groups of genes may be influenced by their chromosomal localization. Chromosome Co-Localization probability calculator (ChroCoLoc) is a publicly available web-based tool for the analysis of co-localization of co-expressed genes identified by microarray experiments. AVAILABILITY: http://www.ebi.ac.uk/expressionprofiler/

Algorithms↗

Fusing microarray experiments with multivariate regression.

MOTIVATION: It is widely acknowledged that microarray data are subject to high noise levels and results are often platform dependent. Therefore, microarray experiments should be replicated several times and in several laboratories before the results can be relied upon. To make the best use of such extensive datasets, methods for microarray data fusion are required. Ideally, the fused data should distil important aspects of the data while suppressing unwanted sources of variation and be amenable to further informal and formal methods of analysis. Also, the variability in the quality of experimentation should be taken into account. RESULTS: We present such an approach to data fusion, based on multivariate regression. We apply our methodology to data from a previous study on cell-cycle control in Schizosaccharomyces pombe. AVAILABILITY: The algorithm implemented in R is freely available from the authors on request.

Algorithms↗

A new algorithm for comparing and visualizing relationships between hierarchical and flat gene expression data clusterings.

MOTIVATION: Clustering is one of the most widely used methods in unsupervised gene expression data analysis. The use of different clustering algorithms or different parameters often produces rather different results on the same data. Biological interpretation of multiple clustering results requires understanding how different clusters relate to each other. It is particularly non-trivial to compare the results of a hierarchical and a flat, e.g. k-means, clustering. RESULTS: We present a new method for comparing and visualizing relationships between different clustering results, either flat versus flat, or flat versus hierarchical. When comparing a flat clustering to a hierarchical clustering, the algorithm cuts different branches in the hierarchical tree at different levels to optimize the correspondence between the clusters. The optimization function is based on graph layout aesthetics or on mutual information. The clusters are displayed using a bipartite graph where the edges are weighted proportionally to the number of common elements in the respective clusters and the weighted number of crossings is minimized. The performance of the algorithm is tested using simulated and real gene expression data. The algorithm is implemented in the online gene expression data analysis tool Expression Profiler. AVAILABILITY: http://www.ebi.ac.uk/expressionprofiler

Algorithms↗

BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis.

biomaRt is a new Bioconductor package that integrates BioMart data resources with data analysis software in Bioconductor. It can annotate a wide range of gene or gene product identifiers (e.g. Entrez-Gene and Affymetrix probe identifiers) with information such as gene symbol, chromosomal coordinates, Gene Ontology and OMIM annotation. Furthermore biomaRt enables retrieval of genomic sequences and single nucleotide polymorphism information, which can be used in data analysis. Fast and up-to-date data retrieval is possible as the package executes direct SQL queries to the BioMart databases (e.g. Ensembl). The biomaRt package provides a tight integration of large, public or locally installed BioMart databases with data analysis in Bioconductor creating a powerful environment for biological data mining.

Algorithms↗

Modelling gene networks at different organisational levels.

Approaches to modelling gene regulation networks can be categorized, according to increasing detail, as network parts lists, network topology models, network control logic models, or dynamic models. We discuss the current state of the art for each of these approaches. There is a gap between the parts list and topology models on one hand, and control logic and dynamic models on the other hand. The first two classes of models have reached a genome-wide scale, while for the other model classes high throughput technologies are yet to make a major impact.

Algorithms↗

Plant-based microarray data at the European Bioinformatics Institute. Introducing AtMIAMExpress, a submission tool for Arabidopsis gene expression data to ArrayExpress.

ArrayExpress is a public microarray repository founded on the Minimum Information About a Microarray Experiment (MIAME) principles that stores MIAME-compliant gene expression data. Plant-based data sets represent approximately one-quarter of the experiments in ArrayExpress. The majority are based on Arabidopsis (Arabidopsis thaliana); however, there are other data sets based on Triticum aestivum, Hordeum vulgare, and Populus subsp. AtMIAMExpress is an open-source Web-based software application for the submission of Arabidopsis-based microarray data to ArrayExpress. AtMIAMExpress exports data in MAGE-ML format for upload to any MAGE-ML-compliant application, such as J-Express and ArrayExpress. It was designed as a tool for users with minimal bioinformatics expertise, has comprehensive help and user support, and represents a simple solution to meeting the MIAME guidelines for the Arabidopsis community. Plant data are queryable both in ArrayExpress and in the Data Warehouse databases, which support queries based on gene-centric and sample-centric annotation. The AtMIAMExpress submission tool is available at http://www.ebi.ac.uk/at-miamexpress/. The software is open source and is available from http://sourceforge.net/projects/miamexpress/. For information, contact miamexpress@ebi.ac.uk.

Academies and Institutes↗

Reconstruction of gene regulatory networks under the finite state linear model.

We study the Finite State Linear Model (FSLM) for modelling gene regulatory networks proposed by A. Brazma and T. Schlitt in [4]. The model incorporates biologically intuitive gene regulatory mechanism similar to that in Boolean networks, and can describe also the continuous changes in protein levels. We consider several theoretical properties of this model; in particular we show that the problem whether a particular gene will reach an active state is algorithmically unsolvable. This imposes some practical difficulties in simulation and reverse engineering of FSLM networks. Nevertheless, our simulation experiments show that sufficiently many of FSLM networks exhibit a regular behaviour and that the model is still quite adequate to describe biological reality. We also propose a comparatively efficient O(2(K)n(K+1)M(2K)m log m) time algorithm for reconstruction of FSLM networks from experimental data. Experiments on reconstruction of random networks are performed to estimate the running time of the algorithm in practice, as well as the number of measurements needed for successful network reconstruction.

Algorithms↗

The ArrayExpress gene expression database: a software engineering and implementation perspective.

MOTIVATION: The lack of microarray data management systems and databases is still one of the major problems faced by many life sciences laboratories. While developing the public repository for microarray data ArrayExpress we had to find novel solutions to many non-trivial software engineering problems. Our experience will be both relevant and useful for most bioinformaticians involved in developing information systems for a wide range of high-throughput technologies. RESULTS: ArrayExpress has been online since February 2002, growing exponentially to well over 10,000 hybridizations (as of September 2004). It has been demonstrated that our chosen design and implementation works for databases aimed at storage, access and sharing of high-throughput data. AVAILABILITY: The ArrayExpress database is available at http://www.ebi.ac.uk/arrayexpress/. The software is open source. CONTACT: ugis@ebi.ac.uk.

Algorithms↗