Evaluating Statistical Methods Using Plasmode Data Sets in the Age of Massive Public Databases: An Illustration Using False Discovery Rates

• Published in: PLoS genetics Vol. 4; no. 6; p. e1000098
• Main Authors: Gadbury, Gary L., Xiang, Qinfang, Yang, Lin, Barnes, Stephen, Page, Grier P., Allison, David B.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2008; Public Library of Science (PLoS)
• Subjects: Animals; Biotechnology; Computational Biology; Computer Simulation; Databases, Factual - statistics & numerical data; Estimates; Experiments; Gene expression; Gene Expression Profiling - statistics & numerical data; Genetics and Genomics; Health sciences; Hypotheses; Mathematics; Models, Genetic; Models, Statistical; Molecular Biology; Oligonucleotide Array Sequence Analysis - statistics & numerical data; Rats; Science Policy; Statistical methods; Studies
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000098

Plasmode is a term coined several years ago to describe data sets that are derived from real data but for which some truth is known. Omic techniques, most especially microarray and genomewide association studies, have catalyzed a new zeitgeist of data sharing that is making data and data sets publicly available on an unprecedented scale. Coupling such data resources with a science of plasmode use would allow statistical methodologists to vet proposed techniques empirically (as opposed to only theoretically) and with data that are by definition realistic and representative. We illustrate the technique of empirical statistics by consideration of a common task when analyzing high dimensional data: the simultaneous testing of hundreds or thousands of hypotheses to determine which, if any, show statistical significance warranting follow-on research. The now-common practice of multiple testing in high dimensional experiment (HDE) settings has generated new methods for detecting statistically significant results. Although such methods have heretofore been subject to comparative performance analysis using simulated data, simulating data that realistically reflect data from an actual HDE remains a challenge. We describe a simulation procedure using actual data from an HDE where some truth regarding parameters of interest is known. We use the procedure to compare estimates for the proportion of true null hypotheses, the false discovery rate (FDR), and a local version of FDR obtained from 15 different statistical methods.