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Statistical Analysis of Adsorption Models for Oligonucleotide Microarrays

Author

Listed:
  • Burden Conrad J

    (Australian National University)

  • Pittelkow Yvonne E

    (Australian National University)

  • Wilson Susan R

    (Australian National University)

Abstract

Recent analyses have shown that the relationship between intensity measurements from high density oligonucleotide microarrays and known concentration is non linear. Thus many measurements of so-called gene expression are neither measures of transcript nor mRNA concentration as might be expected.Intensity as measured in such microarrays is a measurement of fluorescent dye attached to probe-target duplexes formed during hybridization of a sample to the probes on the microarray. We develop several dynamic adsorption models relating fluorescent dye intensity to target RNA concentration, the simplest of which is the equilibrium Langmuir isotherm, or hyperbolic response function. Using data from the Affymerix HG-U95A Latin Square experiment, we evaluate various physical models, including equilibrium and non-equilibrium models, by applying maximum likelihood methods. We show that for these data, equilibrium Langmuir isotherms with probe dependent parameters are appropriate. We describe how probe sequence information may then be used to estimate the parameters of the Langmuir isotherm in order to provide an improved measure of absolute target concentration.

Suggested Citation

  • Burden Conrad J & Pittelkow Yvonne E & Wilson Susan R, 2004. "Statistical Analysis of Adsorption Models for Oligonucleotide Microarrays," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 3(1), pages 1-29, December.
    • Handle: RePEc:bpj:sagmbi:v:3:y:2004:i:1:n:35
    DOI: 10.2202/1544-6115.1095
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    Cited by:

    1. Rempala, Grzegorz A. & Pawlikowska, Iwona, 2008. "Limit theorems for hybridization reactions on oligonucleotide microarrays," Journal of Multivariate Analysis, Elsevier, vol. 99(9), pages 2082-2095, October.

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