Bioinformatics FAQ (Frequently Asked Questions) - Glossary of bioinformatics terms

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Robotic technology is employed in the preparation of most arrays. The DNA sequences are bound to a surface such as a nylon membrane or glass slide at precisely defined locations on a grid. Using an alternate method, some arrays are produced using laser lithographic processes and are referred to as biochips or gene chips. The composition of DNA on the arrays is of two general types:

• Oligonucleotides or DNA fragments (approximately 20-25 nucleotide bases). These arrays are frequently used in genotyping experiments. The sequences of alternate gene forms may be included for detection of mutations or normal variants (polymorphisms).
• Complete or partial cDNA (approximately 500-5 000 nucleotide bases). These arrays are generally used for relative gene expression analysis of two or more samples; however, oligonucleotide-based arrays may also be used for these studies.

DNA samples are prepared from the cells or tissues of interest. For genotyping analysis, the sample is genomic DNA. For expression analysis, the sample is cDNA, DNA copies of RNA. The DNA samples are tagged with a radioactive or fluorescent label and applied to the array. Single stranded DNA will bind to a complementary strand of DNA. At positions on the array where the immobilized DNA recognizes a complementary DNA in the sample, binding or hybridization occurs. The labeled sample DNA marks the exact positions on the array where binding occurs, allowing automatic detection. The output consists of a list of hybridization events, indicating the presence or the relative abundance of specific DNA sequences that are present in the sample.

What is a homologue?

"Homology" is a much-misused term and existed in biology long before the notion of protein sequences. Strictly homology cannot be qualified; it is not correct to state that two proteins are "30% homologous" with each other, for example. If we could look back far enough in the evolutionary histories of any two molecules under comparison, we would be guaranteed to find a common ancestor eventually, but this is not true homology. An example of this would be the relationship between two variants of a single ancestral enzyme resulting from a gene duplication event.

"The classic molecular example is the parallel evolution of amino acid sequences in the lysozyme enzyme in leaf-eating langur monkeys and in cows. Both animals have independently evolved foregut fermentation using bacteria, and in both cases lysozyme has been recruited to degrade these bacteria. Therefore, langur and cow lysozymes are homologous as genes; however, as digestive enzymes they are not homologous because this functionality was not present in the ancestral lysozyme"

What is an ontology?

Biology is changing from being a descriptive to an analytical science. Accurate and consistent descriptions are, however, vital to analysis. The idea of ontologies has been co-opted from philosophy and artificial intelligence to partition bioinformatic knowledge in a way which can be reliably navigated by computers.

This preprint of a review by Ele Holloway of the European Bioinformatics Institute gives a more detailed insight into the varied approaches to ontologies in bioinformatics by covering a recent meeting on the subject. The final version appears in Comparative and Functional Genomics.

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