Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application

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.

                                            [
  "009:25"
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  "hasEmail": "mailto:info@nih.gov"
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    "title": "Official Government Data Source",
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                                            [
  "gene-expression",
  "microarray-analysis",
  "nih",
  "oligonucleotide-arrays",
  "probe-sensitivity"
]
                                        

                                            [
  "009:033"
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                                            {
  "name": "National Institutes of Health",
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                                            [
  "NIH"
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