AI Article Synopsis
- The study investigates how the characteristics of oligo-probes affect their ability to hybridize specifically to targeted DNA sequences while minimizing unwanted hybridization across the entire genome.
- Researchers defined hybridization specificity as the ratio of target-specific hybridization to genome-wide cross-hybridization and analyzed two types of oligo-probes from a microarray database.
- Findings indicate that certain features, like low duplex stability and G-rich sequences, lead to decreased hybridization specificity, and filtering these 'negative' characteristics can significantly enhance probe design, resulting in probes with twice the specificity.
Article Abstract
Motivation: 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.
Results: 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.
Conclusion: 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.
Contact: shabalin@ncbi.nlm.nih.gov or olga.matveeva@gmail.com
Supplementary Information: Supplementary data are available at Bioinformatics online.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939967 | PMC |
| http://dx.doi.org/10.1093/bioinformatics/btw451 | DOI Listing |
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