Characterization of the expression ratio noise structure in high-density oligonucleotide arrays.
BACKGROUND
High-density oligonucleotide microarrays provide a powerful tool for assessing differential mRNA expression levels. Characterizing the noise resulting from the enzymatic and hybridization steps, called type I noise, is essential for attributing significance measures to the differential expression scores. We introduce scoring functions for expression ratios, and associated quality measures. Both the PM (Perfect Match) probes and PM-MM differentials (MM is the single MisMatch) are considered as raw intensities. We then characterize the log-ratio noise structure using robust estimates of their intensity dependent variance.


RESULTS
We show the relationships between the obtained ratios and their quality measures. The complementarity of PM and PM-MM methods is emphasized by the probe sets signal to noise measures. Using a large set of replicate experiments, we demonstrate that the noise structure in the log-ratios very closely follows a local log-normal distribution for both the PM and PM-MM cases. Therefore, significance relative to the type I noise can be quantified reliably using the local STD. We discuss the intensity dependence of the STD and show that ratio scores >1.25 are significant in the mid- to high-intensity range.


CONCLUSIONS
The ratio noise structure inherent to high-density oligonucleotide arrays can be well described in terms of local log-normal ratio distributions with characteristic intensity dependence. Therefore, robust estimates of the local STD of these distributions provide a simple and powerful way for assessing significance (relative to type I noise) in differential gene expression. This approach will be helpful for improving the reliability of predictions from hybridization experiments in general.
Naef
Felix
F
Mathematical Physics laboratory, Center for Studies in Physics and Biology, The Rockefeller University, 1230 York Ave, NY 10021, USA. felix@funes.rockefeller.edu
Hacker
Coleen R
CR
Patil
Nila
N
Magnasco
Marcelo
M
D015342:DNA Probes; D020869:Gene Expression Profiling / Q000379:methods / Q000592:standards*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards
D015342:DNA Probes