From chemical genomics to chemical proteomics: The power of microarray technology

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Abstract

Microarray technology is a high-throughput screening tool to monitor gene and protein expression-level changes and to study their interactions with other biologically important molecules [1-6]. The advent of nucleic acid and protein microarrays is a major advancement in contemporary chemical genomics and chemical proteomics, including drug discovery, medicinal chemistry, and clinical diagnostics. DNA microarrays with up to tens of thousands of oligonucleotide probes are used to measure changes in gene expression levels, to detect single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), or for genotyping or resequencing. In protein microchip technology, in most instances, planar antibody arrays are used with immobilized, monoclonal, polyclonal, or monospecific antibodies to capture their respective antigens [7-9]. Fluorescent or chemiluminescent methods are used for detection and quantification [10-12]. Another approach of chemical proteomics is the use of reversed phase protein microarrays, where proteins are bound to a solid surface, and antibodies from cell lysates or protein extracts [13-17] are used for their interrogation. Whole-cell arrays utilize immobilized cell surface antigen-specific antibodies, which exclusively bind the corresponding cells, allowing detection of surface proteins of interest without their isolation [18,19]. Other techniques utilize suspension or microbead-based arrays, and more recently, affinity and/or chromatographic surface arrays [20-25]. Protein expression profiling using microarray technology is a logical continuation of gene expression profiling (cDNA and transcriptome), with the goal to shed light on the actual expression products of genes that play roles in specific biological processes, diseases, and responses to drug treatments [26-28]. cDNA microarrays are extensively used to identify gene expression changes, as well as to follow expression patterns at the genome level and in comparative phenotype and/or physiological state studies [29]. However, in most instances, cDNA microarrays do not provide relevant information about protein expression levels, that is, one can draw some conclusion about the properties of the inherited material (mutation, deletion, addition, repeats, translocation, etc.) at the transcriptome level, but apparently no information about their gene products, that is, the proteins [30], and much less about their posttranslational modifications. Indeed, except for some rare cases [31], large differences have been reported between transcriptome and proteome expression levels within the same sample [9,32,33].

Original languageEnglish
Title of host publicationChemical Genomics and Proteomics, Second Edition
PublisherCRC Press
Pages81-121
Number of pages41
ISBN (Electronic)9781439830598
ISBN (Print)9781439830529
DOIs
Publication statusPublished - Jan 1 2013

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)

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