Distribution of words with a predefined range of mismatches to a DNA probe in bacterial genomes.
BACKGROUND
Hybridization of oligonucleotides with longer nucleotide sequences is an essential step in nucleic acid biosynthesis in vitro and in vivo, in oligonucleotide-based diagnostics, and in therapeutic applications of oligonucleotides. A major factor determining sensitivity and selectivity of hybridization is the number of base pair mismatches that occur in an ungapped alignment of the oligonucleotide (probe) and a longer sequence (target).


RESULTS
The k-distance match count between the probe and the target is defined as the number of ungapped alignments between the two sequences that have exactly k mismatches, and the k-neighbor match count is defined as the sum of the j-distance match counts for j between 0 and k. We derive a novel formula for the probability of a k-distance match. This formula is based on the assumption that the target is strand-symmetric Bernoulli text (i.e. nucleotides are independently, identically distributed in the target and satisfy Chargaff's second parity rule). Our model predicts that the GC-content in both the probe and the target significantly affects the match count expectation. The ratio of k-neighbor match counts in two distinct genomes for a given probe is a measure of its specificity. We calculated such ratios for pairs of bacterial genomes with different combinations of length, GC-content and phylogenetic distance. Examination of the extreme values of these ratios indicates that probes with a high discriminative power exist for each tested pair.
Melko
O Michael
OM
Stowers Institute for Medical Research, Kansas City, MO 64110, USA. omm@stowers-institute.org
Mushegian
Arcady R
AR
D020137:Base Pair Mismatch / Q000235:genetics*; D001483:Base Sequence; D017076:Computer-Aided Design; D015342:DNA Probes / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D016680:Genome, Bacterial; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid
D015342:DNA Probes