Abstract
High-density DNA microarrays are useful tools for analyzing sequence changes in DNA samples. Although microarray analysis provides informative signals from a large number of probes, the analysis and interpretation of these signals have certain inherent limitations, namely, complex dependency of signals on the probe sequences and the existence of false signals arising from non-specific binding between probe and target. In this study, we have developed a novel algorithm to detect the single-base substitutions by using microarray data based on a thermodynamic model of hybridization. We modified the thermodynamic model by introducing a penalty for mismatches that represent the effects of substitutions on hybridization affinity. This penalty results in significantly higher detection accuracy than other methods, indicating that the incorporation of hybridization free energy can improve the analysis of sequence variants by using microarray data.
Highlights
High-density oligonucleotide microarrays have recently become widely utilized for analysis of gene expression, and for analysis of genomic sequences [1,2,3]
Microarrays designed for the detection of single-nucleotide polymorphisms (SNPs) have been used in the field of medicine to study genomic sequences and to determine disease susceptibility [4,5,6]
Thermodynamic model of hybridization For the detection of nucleotide substitution, we developed a model to estimate the number of target molecules hybridized to probes based on a Finite Hybridization (FH) model [20,22]
Summary
High-density oligonucleotide microarrays have recently become widely utilized for analysis of gene expression, and for analysis of genomic sequences [1,2,3]. We estimated the decrease of hybridization efficiency in the MM probe by using E’ because the MM probes we designed contain a single mismatch between the probe and target, even when there is no base substitution in the sample genomic DNA.
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