A statistical framework for the design of microarray experiments and effective detection of differential gene expression.
BACKGROUND
Microarray experiments generate a high data volume. However, often due to financial or experimental considerations, e.g. lack of sample, there is little or no replication of the experiments or hybridizations. These factors combined with the intrinsic variability associated with the measurement of gene expression can result in an unsatisfactory detection rate of differential gene expression (DGE). Our motivation was to provide an easy to use measure of the success rate of DGE detection that could find routine use in the design of microarray experiments or in post-experiment assessment.


RESULTS
In this study, we address the problem of both random errors and systematic biases in microarray experimentation. We propose a mathematical model for the measured data in microarray experiments and on the basis of this model present a t-based statistical procedure to determine DGE. We have derived a formula to determine the success rate of DGE detection that takes into account the number of microarrays, the number of genes, the magnitude of DGE, and the variance from biological and technical sources. The formula and look-up tables based on the formula, can be used to assist in the design of microarray experiments. We also propose an ad hoc method for estimating the fraction of non-differentially expressed genes within a set of genes being tested. This will help to increase the power of DGE detection.


BACKGROUND
The functions to calculate the success rate of DGE detection have been implemented as a Java application, which is accessible at http://www.le.ac.uk/mrctox/microarray_lab/Microarray_Softwares/Microarray_Softwares.htm
Zhang
Shu-Dong
SD
MRC Toxicology Unit, Hodgkin Building, Lancaster Road, University of Leicester, Leicester, UK. sdz1@le.ac.uk
Gant
Timothy W
TW
D000465:Algorithms; D003627:Data Interpretation, Statistical; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology*; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011381:Programming Languages; D015203:Reproducibility of Results; D012107:Research Design; D018401:Sample Size; D012680:Sensitivity and Specificity; D012984:Software