title: Optimization of signal-to-noise ratio for efficient microarray probe design.
abstract: Target-specific hybridization depends on oligo-probe characteristics that improve hybridization specificity and minimize genome-wide cross-hybridization. Interplay between specific hybridization and genome-wide cross-hybridization has been insufficiently studied, despite its crucial role in efficient probe design and in data analysis.
  
  
  
  In this study, we defined hybridization specificity as a ratio between oligo target-specific hybridization and oligo genome-wide cross-hybridization. A microarray database, derived from the Genomic Comparison Hybridization (GCH) experiment and performed using the Affymetrix platform, contains two different types of probes. The first type of oligo-probes does not have a specific target on the genome and their hybridization signals are derived from genome-wide cross-hybridization alone. The second type includes oligonucleotides that have a specific target on the genomic DNA and their signals are derived from specific and cross-hybridization components combined together in a total signal. A comparative analysis of hybridization specificity of oligo-probes, as well as their nucleotide sequences and thermodynamic features was performed on the database. The comparison has revealed that hybridization specificity was negatively affected by low stability of the fully-paired oligo-target duplex, stable probe self-folding, G-rich content, including GGG motifs, low sequence complexity and nucleotide composition symmetry.
  
  
  
  Filtering out the probes with defined 'negative' characteristics significantly increases specific hybridization and dramatically decreasing genome-wide cross-hybridization. Selected oligo-probes have two times higher hybridization specificity on average, compared to the probes that were filtered from the analysis by applying suggested cutoff thresholds to the described parameters. A new approach for efficient oligo-probe design is described in our study.
  
  
  
  shabalin@ncbi.nlm.nih.gov or olga.matveeva@gmail.com
  
  
  
  Supplementary data are available at Bioinformatics online.
authors: Biopolymer Design LLC, Acton, MA 01721, USA Engelhardt Institute of Molecular Biology, Moscow 119991, Russia.
authors: Olga V
authors: OV
authors: Matveeva
authors: Engelhardt Institute of Molecular Biology, Moscow 119991, Russia.
authors: Yury D
authors: YD
authors: Nechipurenko
authors: Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russia.
authors: Evgeniy
authors: E
authors: Riabenko
authors: Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072 Australia.
authors: Chikako
authors: C
authors: Ragan
authors: Institute of Mathematical Problems of Biology, Pushchino, Moscow Region, 142290, Russia.
authors: Nafisa N
authors: NN
authors: Nazipova
authors: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
authors: Aleksey Y
authors: AY
authors: Ogurtsov
authors: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
authors: Svetlana A
authors: SA
authors: Shabalina
mesh_terms: D015342:DNA Probes; D020869:Gene Expression Profiling; D016678:Genome; D023281:Genomics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides; D012680:Sensitivity and Specificity; D059629:Signal-To-Noise Ratio
chemical_list: D015342:DNA Probes; D009841:Oligonucleotides