DESIGNING CUSTOMISED GENE EXPRESSION ARRAYS BASED ON SPECIFIC BIOLOGICAL QUESTIONS OR FUNCTIONS

Article type: Research Article

Authors: Khalid, Sabah^; | Grazio, Daniela | Wang, Ping | Liu, Xiaohui | Li, Su-Ling

Affiliations: Molecular Immunology Group, Microarray Facility, Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, UK | Intelligent Data Analysis Group, Department of Information Systems and Computing, Brunel University, Uxbridge, UK | Molecular Immunology Group, Microarray Facility, Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, UK | Immunology Group, Institute of Cell and Molecular Sciences, Barts and London School of Medicine, London, UK | Intelligent Data Analysis Group, Department of Information Systems and Computing, Brunel University, Uxbridge, UK | Molecular Immunology Group, Microarray Facility, Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, UK

Abstract: The declaration "DNA microarrays serve as powerful tools for the global characterization of gene expression" is widely accepted by the scientific community exploiting microarray technology. With the inherent ability to distinguish between the expression levels of genes, microarrays have the power to provide the researcher with a direction for further exploration. However, the immediate results from microarray experiments require further mining to determine the genes, which have been differentially expressed. This narrows down the dataset to those genes that are of most interest to the researcher. In turn, hypotheses regarding the significance of these genes within the molecular mechanism being investigated can be generated. This would result in a more in-depth investigation within the researcher's area of expertise and further microarray experiments. The purpose of these experiments would be to answer more detailed biological questions arising from the analysis of the initial microarray. As a result of the enhanced focus within the investigative area, it would be ideal to use more specialised microarrays facilitating the gain of further knowledge into the biological aspect under scrutiny. Although commercially available, microarrays may be of limited use if they fail to represent the targeted pathways and biological processes to the extent required. Hence, customised microarrays become extremely advantageous, benefiting researchers with particular requirements. Furthermore, due to the sheer cost of DNA gene chips it is impractical to purchase microarrays for every biological need, and thus, it becomes imperative for biologists to maximise the use of existing gene sets. In order to achieve this, bioinformatics tools are necessary to extract meaningful data from the gene set according to a biologist's requirements. To this end, the authors have developed the first software, called Gene Chip Design, which can extract meaningful data from a given gene set according to a biologist's needs. This unique information retrieval software is a powerful, flexible and user-friendly tool aimed at researchers needing to generate personalised custom in-house arrays that represent the genes from specialised biological pathways of interest. With the inbuilt functionality to generate a novel gene chip specific to a researcher's interest from any given generalised gene set, this software can be applied within any biological field. An ontology to allow the global functional characterization of any given gene set, has also been created, together with the unique ability to categorize genes in a more structured and informative manner within numerous functional groups. Furthermore, this software identifies biological pathways pertaining to genes of interest. These aspects also provide researchers with the control to identify further genes with biological functions of interest to extract from their gene set and incorporate into their unique gene chip. Using their NIA 15K Mouse cDNA Clone Gene Set, the authors have designed several gene chips including an oncology gene chip. Furthermore, combined with their previous microarray experimental results, the researchers have developed a novel immuno-tolerance gene chip that can be used for further studies investigating the molecular mechanisms underlying autoimmune disease.

Keywords: oncology, immune tolerance, microarrays, gene chip design, functional annotation, biological pathways

Journal: Journal of Integrated Design & Process Science, vol. 11, no. 3, pp. 69-83, 2007