Real-time DNA Microarrays: Reality Check

Overview

Journal Biochem Soc Trans

Specialty Biochemistry

Date 2009 Mar 18

PMID 19290884

Citations 5

Authors

Alexander Chagovetz

Steve Blair

Affiliations

Soon will be listed here.

Abstract

DNA microarrays are plagued with inconsistent quantifications and false-positive results. Using established mechanisms of surface reactions, we argue that these problems are inherent to the current technology. In particular, the problem of multiplex non-equilibrium reactions cannot be resolved within the framework of the existing paradigm. We discuss the advantages and limitations of changing the paradigm to real-time data acquisition similar to real-time PCR methodology. Our analysis suggests that the fundamental problem of multiplex reactions is not resolved by the real-time approach itself. However, by introducing new detection chemistries and analysis approaches, it is possible to extract target-specific quantitative information from real-time microarray data. The possible scope of applications for real-time microarrays is discussed.

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References

Okoniewski M, Miller C . Hybridization interactions between probesets in short oligo microarrays lead to spurious correlations. BMC Bioinformatics. 2006; 7:276. PMC: 1513401. DOI: 10.1186/1471-2105-7-276. View

Chan V, Graves D, McKenzie S . The biophysics of DNA hybridization with immobilized oligonucleotide probes. Biophys J. 1995; 69(6):2243-55. PMC: 1236463. DOI: 10.1016/S0006-3495(95)80095-0. View

Graves D . Powerful tools for genetic analysis come of age. Trends Biotechnol. 1999; 17(3):127-34. DOI: 10.1016/s0167-7799(98)01241-4. View

Rule R, Pozhitkov A, Noble P . Use of hidden correlations in short oligonucleotide array data are insufficient for accurate quantification of nucleic acid targets in complex target mixtures. J Microbiol Methods. 2008; 76(2):188-95. DOI: 10.1016/j.mimet.2008.10.011. View

Southern E . Tools for genomics. Nat Med. 2005; 11(10):1029-34. DOI: 10.1038/nm1005-1029. View

Pozhitkov A, Rule R, Stedtfeld R, Hashsham S, Noble P . Concentration dependency of nonequilibrium thermal dissociation curves in complex target samples. J Microbiol Methods. 2008; 74(2-3):82-8. DOI: 10.1016/j.mimet.2008.03.010. View

Chu L, Forch R, Knoll W . Surface-plasmon-enhanced fluorescence spectroscopy for DNA detection using fluorescently labeled PNA as "DNA indicator". Angew Chem Int Ed Engl. 2007; 46(26):4944-7. DOI: 10.1002/anie.200605247. View

Pozhitkov A, Noble P . High variability in melting profiles from gel pad arrays. Environ Microbiol. 2007; 9(7):1865. DOI: 10.1111/j.1462-2920.2007.01296.x. View

Housby J, Southern E . Thermus scotoductus and Rhodothermus marinus DNA ligases have higher ligation efficiencies than thermus thermophilus DNA ligase. Anal Biochem. 2002; 302(1):88-94. DOI: 10.1006/abio.2001.5532. View

10.

Piunno P, Krull U . Trends in the development of nucleic acid biosensors for medical diagnostics. Anal Bioanal Chem. 2005; 381(5):1004-11. DOI: 10.1007/s00216-004-3024-0. View

11.

Lipshutz R, Fodor S, Gingeras T, Lockhart D . High density synthetic oligonucleotide arrays. Nat Genet. 1999; 21(1 Suppl):20-4. DOI: 10.1038/4447. View

12.

Marcelino L, Backman V, Donaldson A, Steadman C, Thompson J, Preheim S . Accurately quantifying low-abundant targets amid similar sequences by revealing hidden correlations in oligonucleotide microarray data. Proc Natl Acad Sci U S A. 2006; 103(37):13629-34. PMC: 1559406. DOI: 10.1073/pnas.0601476103. View

13.

Korkola J, Estep A, Pejavar S, DeVries S, Jensen R, Waldman F . Optimizing stringency for expression microarrays. Biotechniques. 2003; 35(4):828-35. DOI: 10.2144/03354mt04. View

14.

Hackl H, Sanchez Cabo F, Sturn A, Wolkenhauer O, Trajanoski Z . Analysis of DNA microarray data. Curr Top Med Chem. 2004; 4(13):1357-70. DOI: 10.2174/1568026043387773. View

15.

Zhang L, Miles M, Aldape K . A model of molecular interactions on short oligonucleotide microarrays. Nat Biotechnol. 2003; 21(7):818-21. DOI: 10.1038/nbt836. View

16.

Sorokin N, Yurasov D, Cherepanov A, Kozhekbaeva J, Chechetkin V, Gra O . Effects of external transport on discrimination between perfect and mismatch duplexes on gel-based oligonucleotide microchips. J Biomol Struct Dyn. 2007; 24(6):571-8. DOI: 10.1080/07391102.2007.10507146. View

17.

Yang C, Hsiao C, Chou C . Evaluation of experimental designs for two-color cDNA microarrays. J Comput Biol. 2005; 12(9):1202-20. DOI: 10.1089/cmb.2005.12.1202. View

18.

Bishop J, Chagovetz A, Blair S . Kinetics of multiplex hybridization: mechanisms and implications. Biophys J. 2007; 94(5):1726-34. PMC: 2242776. DOI: 10.1529/biophysj.107.121459. View

19.

Naef F, Lim D, Patil N, Magnasco M . DNA hybridization to mismatched templates: a chip study. Phys Rev E Stat Nonlin Soft Matter Phys. 2002; 65(4 Pt 1):040902. DOI: 10.1103/PhysRevE.65.040902. View

20.

Ye Y, Chen L, Liu X, Krull U . DNA and microfluidics: building molecular electronics systems. Anal Chim Acta. 2007; 568(1-2):138-45. DOI: 10.1016/j.aca.2005.11.080. View