Abstract:
Many applications in modern biotechnology require a rapid and sensitive prediction of hybridization or partial hybridization between an oligonucleotide and potential targets in a genomic DNA or mRNA database. In addition, the accurate prediction of melting profiles between an oligonucleotide and a target nucleic acid is also of great value. DNA and RNA chip technologies [16, 17], PCR primer design, sequencing by hybridization and gene diagnostic methods, including SNP detection, are all technologies for which these predictions are very important. DNA chips alone have numerous applications. They are useful to monitor whole genome gene expression [15]. They are well adapted to the detection of single nucleotide polymorphisms (SNPs) [8], to identifying organisms from their sequences [2] or the characterization of splicing variants [5]. They can be used for DNA sequencing [3] or to search for protein target sites on DNA [7]. Computational methods for hybridization and melting prediction tend to make use of existing tools. Thus the very well-known BLAST [1] program is used for database searching to determine oligonucleotide specificity. BLAST or MegaBLAST are inappropriate methods since they were designed to search for similarity based on an evolutionary model rather than hybridization based on equilibrium thermodynamics. Similarly, melting temperatures for folded, single stranded oligonucleotides, or hybridized
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