ArticleBioinformatics (Oxford, England)2016
Optimization of signal-to-noise ratio for efficient microarray probe design.
Article in Bioinformatics (Oxford, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed.
- Review
- NNDB: An Expanded Database of Nearest Neighbor Parameters for Predicting Stability of Nucleic Acid Secondary Structures.Journal of molecular biology · 2024Article
- FREQ-Seq2: a method for precise high-throughput combinatorial quantification of allele frequencies.G3 (Bethesda, Md.) · 2023Article
- Understanding off-target effects through hybridization kinetics and thermodynamics.Cell biology and toxicology · 2020Article
- A decision-theoretic approach to the evaluation of machine learning algorithms in computational drug discovery.Bioinformatics (Oxford, England) · 2019Article
- Ultraconserved element (UCE) probe set design: Base genome and initial design parameters critical for optimization.Ecology and evolution · 2019Article
- Sequence characteristics define trade-offs between on-target and genome-wide off-target hybridization of oligoprobes.PloS one · 2018Article
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7 authors.
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Abstract
motivationTarget-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.
resultsIn 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.
conclusionFiltering 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. CONTACT: shabalin@ncbi.nlm.nih.gov or olga.matveeva@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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