Potential Bias in GO::TermFinder

• Published in: Briefings in bioinformatics Vol. 10; no. 3; pp. 289 - 294
• Main Authors: Flight, Robert M., Wentzell, Peter D.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2009; Oxford Publishing Limited (England)
• Subjects: Algorithms; Bias; Bioinformatics; Computational Biology - methods; Databases, Genetic; Estimating techniques; Gene Expression Profiling - methods; Information Storage and Retrieval - methods; Oligonucleotide Array Sequence Analysis - methods; Samples; Software; gene ontology; enrichment; GO::Termfinder; false discovery rate; bias
• ISSN: 1467-5463; 1477-4054
• DOI: 10.1093/bib/bbn054

The increased need for multiple statistical comparisons under conditions of non-independence in bioinformatics applications, such as DNA microarray data analysis, has led to the development of alternatives to the conventional Bonferroni correction for adjusting P-values. The use of the false discovery rate (FDR), in particular, has grown considerably. However, the calculation of the FDR frequently depends on drawing random samples from a population, and inappropriate sampling will result in a bias in the calculated FDR. In this work, we demonstrate a bias due to incorrect random sampling in the widely used GO::TermFinder package. Both T2 and permutation tests are used to confirm the bias for a test set of data, which leads to an overestimation of the FDR of about 10%. A simple fix to the random sampling method is proposed to remove the bias.