PLoS One. 2015 Apr 30;10(4):e0125081. doi: 10.1371/journal.pone.0125081. eCollection 2015.
PloS one
Matthew W Mitchell
PMID: 25927705 PMCID: PMC4415974 DOI: 10.1371/journal.pone.0125081
For pathway analysis of genomic data, the most common methods involve combining p-values from individual statistical tests. However, there are several multivariate statistical methods that can be used to test whether a pathway has changed. Because of the large number of variables and pathway sizes in genomics data, some of these statistics cannot be computed. However, in metabolomics data, the number of variables and pathway sizes are typically much smaller, making such computations feasible. Of particular interest is being able to detect changes in pathways that may not be detected for the individual variables. We compare the performance of both the p-value methods and multivariate statistics for self-contained tests with an extensive simulation study and a human metabolomics study. Permutation tests, rather than asymptotic results are used to assess the statistical significance of the pathways. Furthermore, both one and two-sided alternatives hypotheses are examined. From the human metabolomic study, many pathways were statistically significant, although the majority of the individual variables in the pathway were not. Overall, the p-value methods perform at least as well as the multivariate statistics for these scenarios.
