A hidden Markov tree model for testing multiple hypotheses corresponding to Gene Ontology gene sets

Abstract

Abstract Background Testing predefined gene categories has become a common practice for scientists analyzing high throughput transcriptome data. A systematic way of testing gene categories leads to testing hundreds of null hypotheses that correspond to nodes in a directed acyclic graph. The relationships among gene categories induce logical restrictions among the corresponding null hypotheses. An existing fully Bayesian method is powerful but computationally demanding. Results We develop a computationally efficient method based on a hidden Markov tree model (HMTM). Our method is several orders of magnitude faster than the existing fully Bayesian method. Through simulation and an expression quantitative trait loci study, we show that the HMTM method provides more powerful results than other existing methods that honor the logical restrictions. Conclusions The HMTM method provides an individual estimate of posterior probability of being differentially expressed for each gene set, which can be useful for result interpretation. The R package can be found on https://github.com/k22liang/HMTGO.

Keywords

• Differential expression
• Directed acyclic graph
• Expectation maximization
• Expression quantitative trait loci
• False discovery rate
• Gene set enrichment analysis