title: Development of a physical model-based algorithm for the detection of single-nucleotide substitutions by using tiling microarrays.
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.
authors: Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors: Naoaki
authors: N
authors: Ono
authors: Shingo
authors: S
authors: Suzuki
authors: Chikara
authors: C
authors: Furusawa
authors: Hiroshi
authors: H
authors: Shimizu
authors: Tetsuya
authors: T
authors: Yomo
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity
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