An improved procedure for gene selection from microarray experiments using false discovery rate criterion.
BACKGROUND
A large number of genes usually show differential expressions in a microarray experiment with two types of tissues, and the p-values of a proper statistical test are often used to quantify the significance of these differences. The genes with small p-values are then picked as the genes responsible for the differences in the tissue RNA expressions. One key question is what should be the threshold to consider the p-values small. There is always a trade off between this threshold and the rate of false claims. Recent statistical literature shows that the false discovery rate (FDR) criterion is a powerful and reasonable criterion to pick those genes with differential expression. Moreover, the power of detection can be increased by knowing the number of non-differential expression genes. While this number is unknown in practice, there are methods to estimate it from data. The purpose of this paper is to present a new method of estimating this number and use it for the FDR procedure construction.


RESULTS
A combination of test functions is used to estimate the number of differentially expressed genes. Simulation study shows that the proposed method has a higher power to detect these genes than other existing methods, while still keeping the FDR under control. The improvement can be substantial if the proportion of true differentially expressed genes is large. This procedure has also been tested with good results using a real dataset.


CONCLUSIONS
For a given expected FDR, the method proposed in this paper has better power to pick genes that show differentiation in their expression than two other well known methods.
Yang
James J
JJ
Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, Detroit, Michigan, USA. jyang2@hfhs.org
Yang
Mark C K
MC
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005189:False Positive Reactions; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins