EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments

• DOI: 10.1371/journal.pone.0187287
• Publication Date: 2017-10-31T18:25:33Z
• Authors: Sinjini Sikdar; Somnath Datta; Susmita Datta
• Keywords: 0303 health sciences; Lung Neoplasms; Models, Statistical; Science; Q; Statistics as Topic; R; Gene Expression; Genomics; Empirical Research; 03 medical and health sciences; Genes; Meta-Analysis as Topic; Data Interpretation, Statistical; Medicine; Humans; Research Article; Oligonucleotide Array Sequence Analysis

Recent developments in high throughput genomic assays have opened up the possibility of testing hundreds and thousands of genes simultaneously. However, adhering to the regular statistical assumptions regarding the null distributions of test statistics in such large-scale multiple testing frameworks has the potential of leading to incorrect significance testing results and biased inference. This problem gets worse when one combines results from different independent genomic experiments with a possibility of ending up with gross false discoveries of significant genes. In this article, we develop a meta-analysis method of combining p-values from different independent experiments involving large-scale multiple testing frameworks, through empirical adjustments of the individual test statistics and p-values. Even though, it is based on various existing ideas, this specific combination is novel and potentially useful. Through simulation studies and real genomic datasets we show that our method outperforms the standard meta-analysis approach of significance testing in terms of accurately identifying the truly significant set of genes.