DMCA
Model-Based Analysis of Oligonucleotide Arrays: Model Validation, Design Issues and Standard Error Application (2001)
| Citations: | 774 - 28 self |
BibTeX
@MISC{Li01model-basedanalysis,
author = {Cheng Li and Wing Hung Wong},
title = {Model-Based Analysis of Oligonucleotide Arrays: Model Validation, Design Issues and Standard Error Application},
year = {2001}
}
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Abstract
Background: A model-based analysis of oligonucleotide expression arrays we developed previously uses a probe-sensitivity index to capture the response characteristic of a specific probe pair and calculates model-based expression indexes (MBEI). MBEI has standard error attached to it as a measure of accuracy. Here we investigate the stability of the probe-sensitivity index across different tissue types, the reproducibility of results in replicate experiments, and the use of MBEI in perfect match (PM)-only arrays. Results: Probe-sensitivity indexes are stable across tissue types. The target gene's presence in many arrays of an array set allows the probe-sensitivity index to be estimated accurately. We extended the model to obtain expression values for PM-only arrays, and found that the 20-probe PM-only model is comparable to the 10-probe PM/MM difference model, in terms of the expression correlations with the original 20-probe PM/MM difference model. MBEI method is able to extend the reliable detection limit of expression to a lower mRNA concentration. The standard errors of MBEI can be used to construct confidence intervals of fold changes, and the lower confidence bound of fold change is a better ranking statistic for filtering genes. We can assign reliability indexes for genes in a specific cluster of interest in hierarchical clustering by resampling clustering trees. A software dChip implementing many of these analysis methods is made available. Conclusions: The model-based approach reduces the variability of low expression estimates, and provides a natural method of calculating expression values for PM-only arrays. The standard errors attached to expression values can be used to assess the reliability of downstream analysis. Published: X Month 2001 Genome Biology...
Keyphrases
probe-sensitivity index model-based analysis oligonucleotide array standard error application model validation design issue expression value pm-only array fold change standard error specific cluster many array low expression estimate mbei method expression correlation confidence bound specific probe pair tissue type hierarchical clustering model-based expression index different tissue type reliability index reliable detection limit 20-probe pm-only model 10-probe pm mm difference model genome biology mrna concentration perfect match analysis method software dchip confidence interval target gene downstream analysis natural method array set ranking statistic oligonucleotide expression model-based approach replicate experiment response characteristic
