Empirical study of supervised gene screening.
BACKGROUND
Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1) unsupervised gene screening; (2) supervised gene screening; and (3) statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods.


RESULTS
We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened.


CONCLUSIONS
From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1) genes passed different supervised screenings may be considerably different; (2) concordance may vary, depending on the underlying data structure and percentage of selected genes; (3) evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4) concordance cannot be improved by supervised screening based on reproducibility.
Ma
Shuangge
S
Department of Epidemiology and Public Health, Yale University, New Haven, CT 06520, USA. shuangge.ma@yale.edu
D001185:Artificial Intelligence; D014408:Biomarkers, Tumor / Q000235:genetics*; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins