A classification of tasks for the systematic study of immune response using functional genomics data.

A full understanding of the immune system and its responses to infection by different pathogens is important for the development of anti-parasitic vaccines. A growing number of large-scale experimental techniques, such as microarrays, are being used to gain a better understanding of the immune system. To analyse the data generated by these experiments, methods such as clustering are widely used. However, individual applications of these methods tend to analyse the experimental data without taking publicly available biological and immunological knowledge into account systematically and in an unbiased manner. To make best use of the experimental investment, to benefit from existing evidence, and to support the findings in the experimental data, available biological information should be included in the analysis in a systematic manner. In this review we present a classification of tasks that shows how experimental data produced by studies of the immune system can be placed in a broader biological context. Taking into account available evidence, the classification can be used to identify different ways of analysing the experimental data systematically. We have used the classification to identify alternative ways of analysing microarray data, and illustrate its application using studies of immune responses in mice to infection with the intestinal nematode parasites Trichuris muris and Heligmosomoides polygyrus.

Identification of novel genes in intestinal tissue that are regulated after infection with an intestinal nematode parasite.

Infection of resistant or susceptible mice with Trichuris muris provokes mesenteric lymph node responses which are polarized towards Th2 or Th1, respectively. These responses are well documented in the literature. In contrast, little is known about the local responses occurring within the infected intestine. Through microarray analyses, we demonstrate that the gene expression profile of infected gut tissue differs according to whether the parasite is expelled or not. Genes differentially regulated postinfection in resistant BALB/c mice include several antimicrobial genes, in particular, intelectin (Itln). In contrast, analyses in AKR mice which ultimately progress to chronic infection provide evidence for a Th1-dominated mucosa with up-regulated expression of genes regulated by gamma interferon. Increases in the expression of genes associated with tryptophan metabolism were also apparent with the coinduction of tryptophanyl tRNA synthetase (Wars) and indoleamine-2,3-dioxygenase (Indo). With the emerging literature on the role of these gene products in the suppression of T-cell responses in vitro and in vivo, their up-regulated expression here may suggest a role for tryptophan metabolism in the parasite survival strategy.

CADRE: the Central Aspergillus Data REpository.

CADRE is a public resource for housing and analysing genomic data extracted from species of Aspergillus. It arose to enable maintenance of the complete annotated genomic sequence of Aspergillus fumigatus and to provide tools for searching, analysing and visualizing features of fungal genomes. By implementing CADRE using Ensembl, a framework is in place for storing and comparing several genomes: the resource will thus expand by including other Aspergillus genomes (such as Aspergillus nidulans) as they become available. CADRE is accessible at http://www.cadre. man.ac.uk.

Conceptual modelling of genomic information.

MOTIVATION: Genome sequencing projects are making available complete records of the genetic make-up of organisms. These core data sets are themselves complex, and present challenges to those who seek to store, analyse and present the information. However, in addition to the sequence data, high throughput experiments are making available distinctive new data sets on protein interactions, the phenotypic consequences of gene deletions, and on the transcriptome, proteome, and metabolome. The effective description and management of such data is of considerable importance to bioinformatics in the post-genomic era. The provision of clear and intuitive models of complex information is surprisingly challenging, and this paper presents conceptual models for a range of important emerging information resources in bioinformatics. It is hoped that these can be of benefit to bioinformaticians as they attempt to integrate genetic and phenotypic data with that from genomic sequences, in order to both assign gene functions and elucidate the different pathways of gene action and interaction. RESULTS: This paper presents a collection of conceptual (i.e. implementation-independent) data models for genomic data. These conceptual models are amenable to (more or less direct) implementation on different computing platforms.

TAMBIS: transparent access to multiple bioinformatics information sources.

UNLABELLED: TAMBIS (Transparent Access to Multiple Bioinformatics Information Sources) is an application that allows biologists to ask rich and complex questions over a range of bioinformatics resources. It is based on a model of the knowledge of the concepts and their relationships in molecular biology and bioinformatics. AVAILABILITY: TAMBIS is available as an applet from http://img.cs.man.ac.uk/tambis SUPPLEMENTARY: A full manual, tutorial and videos can be found at http://img.cs.man.ac.uk/tambis. CONTACT: tambis@cs.man.ac.uk

An ontology for bioinformatics applications.

MOTIVATION: An ontology of biological terminology provides a model of biological concepts that can be used to form a semantic framework for many data storage, retrieval and analysis tasks. Such a semantic framework could be used to underpin a range of important bioinformatics tasks, such as the querying of heterogeneous bioinformatics sources or the systematic annotation of experimental results. RESULTS: This paper provides an overview of an ontology [the Transparent Access to Multiple Biological Information Sources (TAMBIS) ontology or TaO] that describes a wide range of bioinformatics concepts. The present paper describes the mechanisms used for delivering the ontology and discusses the ontology's design and organization, which are crucial for maintaining the coherence of a large collection of concepts and their relationships. AVAILABILITY: The TAMBIS system, which uses a subset of the TaO described here, is accessible over the Web via http://img.cs.man.ac.uk/tambis (although in the first instance, we will use a password mechanism to limit the load on our server). The complete model is also available on the Web at the above URL.

An object-oriented database for protein structure analysis.

An object-oriented database system has been developed which is being used to store protein structure data. The database can be queried using the logic programming language Prolog or the query language Daplex. Queries retrieve information by navigating through a network of objects which represent the primary, secondary and tertiary structures of proteins. Routines written in both Prolog and Daplex can integrate complex calculations with the retrieval of data from the database, and can also be stored in the database for sharing among users. Thus object-oriented databases are better suited to prototyping applications and answering complex queries about protein structure than relational databases. This system has been used to find loops of varying length and anchor positions when modelling homologous protein structures.