Statistical analysis of adsorption models for oligonucleotide microarrays

Statistical Applications in Genetics and Molecular Biology
Conrad J BurdenSusan R Wilson

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.

Citations

Jun 1, 2010·BMC Bioinformatics·Hans BinderConrad J Burden
Dec 3, 2008·BMC Bioinformatics·Thomas NaiserAlbrecht Ott
Sep 2, 2008·Algorithms for Molecular Biology : AMB·Hans Binder, Stephan Preibisch
May 15, 2008·PloS One·Crystal JaingTom Slezak
Nov 20, 2009·PloS One·Hans BinderTorsten Glomb
Nov 2, 2014·Applied Microbiology and Biotechnology·Daniel R NogueraL Safak Yilmaz
Mar 5, 2008·Genes, Chromosomes & Cancer·Lindsay A BrownDavid G Huntsman
Jul 22, 2014·Statistics in Medicine·Maral Saadati, Axel Benner
Feb 13, 2014·The Review of Scientific Instruments·Alexander BadalyanAbbas Zeinijahromi
Aug 29, 2006·Nucleic Acids Research·Diana AbduevaSimon Tavaré
Jun 15, 2007·Nucleic Acids Research·Dmitriy SkvortsovSimon Tavaré
Aug 8, 2018·Journal of Biomolecular Structure & Dynamics·Y V StirmanovY D Nechipurenko
Nov 4, 2011·Psychosomatic Medicine·R Gina SilversteinWilloughby B Britton

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