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      BOND: Basic OligoNucleotide Design

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          Abstract

          Background

          DNA microarrays have become ubiquitous in biological and medical research. The most difficult problem that needs to be solved is the design of DNA oligonucleotides that (i) are highly specific, that is, bind only to the intended target, (ii) cover the highest possible number of genes, that is, all genes that allow such unique regions, and (iii) are computed fast. None of the existing programs meet all these criteria.

          Results

          We introduce a new approach with our software program BOND (Basic OligoNucleotide Design). According to Kane’s criteria for oligo design, BOND computes highly specific DNA oligonucleotides, for all the genes that admit unique probes, while running orders of magnitude faster than the existing programs. The same approach enables us to introduce also an evaluation procedure that correctly measures the quality of the oligonucleotides. Extensive comparison is performed to prove our claims. BOND is flexible, easy to use, requires no additional software, and is freely available for non-commercial use from http://www.csd.uwo.ca/∼ilie/BOND/.

          Conclusions

          We provide an improved solution to the important problem of oligonucleotide design, including a thorough evaluation of oligo design programs. We hope BOND will become a useful tool for researchers in biological and medical sciences by making the microarray procedures faster and more accurate.

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          Most cited references30

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          A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics.

          A unified view of polymer, dumbbell, and oligonucleotide nearest-neighbor (NN) thermodynamics is presented. DNA NN DeltaG degrees 37 parameters from seven laboratories are presented in the same format so that careful comparisons can be made. The seven studies used data from natural polymers, synthetic polymers, oligonucleotide dumbbells, and oligonucleotide duplexes to derive NN parameters; used different methods of data analysis; used different salt concentrations; and presented the NN thermodynamics in different formats. As a result of these differences, there has been much confusion regarding the NN thermodynamics of DNA polymers and oligomers. Herein I show that six of the studies are actually in remarkable agreement with one another and explanations are provided in cases where discrepancies remain. Further, a single set of parameters, derived from 108 oligonucleotide duplexes, adequately describes polymer and oligomer thermodynamics. Empirical salt dependencies are also derived for oligonucleotides and polymers.
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            Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer.

            We describe a flexible system for gene expression profiling using arrays of tens of thousands of oligonucleotides synthesized in situ by an ink-jet printing method employing standard phosphoramidite chemistry. We have characterized the dependence of hybridization specificity and sensitivity on parameters including oligonucleotide length, hybridization stringency, sequence identity, sample abundance, and sample preparation method. We find that 60-mer oligonucleotides reliably detect transcript ratios at one copy per cell in complex biological samples, and that ink-jet arrays are compatible with several different sample amplification and labeling techniques. Furthermore, results using only a single carefully selected oligonucleotide per gene correlate closely with those obtained using complementary DNA (cDNA) arrays. Most of the genes for which measurements differ are members of gene families that can only be distinguished by oligonucleotides. Because different oligonucleotide sequences can be specified for each array, we anticipate that ink-jet oligonucleotide array technology will be useful in a wide variety of DNA microarray applications.
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              Suffix Arrays: A New Method for On-Line String Searches

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                Author and article information

                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central
                1471-2105
                2013
                27 February 2013
                : 14
                : 69
                Affiliations
                [1 ]Department of Computer Science, University of Western Ontario, London, ON, N6A5B7, Canada
                [2 ]Department of Computing and Software, McMaster University, Hamilton, ON, L8S 4K1, Canada
                [3 ]Department of Biology, McMaster University, Hamilton, ON, L8S 4K1, Canada
                Article
                1471-2105-14-69
                10.1186/1471-2105-14-69
                3648450
                23444904
                f9a40f03-81d8-4b0c-b61b-a7003e841465
                Copyright ©2013 Ilie et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 August 2012
                : 21 February 2013
                Categories
                Research Article

                Bioinformatics & Computational biology
                dna oligonucleotide design,microarray,spaced seeds
                Bioinformatics & Computational biology
                dna oligonucleotide design, microarray, spaced seeds

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