Published online Nov 26, 2014. doi: 10.13105/wjma.v2.i4.179
Revised: October 16, 2014
Accepted: October 28, 2014
Published online: November 26, 2014
AIM: To propose a new meta-analysis method for bivariate P value which account for the paired structure.
METHODS: Studies that look to test two different features from the same sample gives rise to bivariate P value. A relevant example of this is testing for periodicity as well expression from time-course gene expression studies. Kocak et al (2010) uses George and Mudholkar’ (1983) “Difference of Two Logit-Sums” method to pool bivariate P value across independent experiments, assuming independence within a pair. As bivariate P value need not to be independent within a given study, we propose a new meta-analysis approach for pooling bivariate P value across independent experiments, which accounts for potential correlation between paired P-values. We compare the “Difference of Two Logit Sums”method with our novel approach in terms of their sensitivity and specificity through extensive simulations by generating P value samples from most commonly used tests namely, Z test, t test, chi-square test, and F test, with varying sample sizes and correlation structure.
RESULTS: The simulations results showed that our new meta-analysis approach for correlated and uncorrelated bivariate P value has much more desirable sensitivity and specificity features compared to the existing method, which treats each member of the paired P value as independent. We also compare these meta-analysis approaches on bivariate P value from periodicity and expression tests of 4936 S.Pombe genes from 10 independent time-course experiments and we showed that our new approach ranks the periodic, conserved, and cycling genes significantly higher, and detects many more periodic, “conserved” and “cycling” genes among the top 100 genes, compared to the ‘Difference of Two Logit-Sums’ method. Finally, we used our meta-analytic approach to compare the relative evidence in the association of pre-term birth with preschool wheezing versus pre-school asthma.
CONCLUSION: The new meta-analysis method has much better sensitivity and specific characteristics compared to the “Difference of Two-Logit Sums” method and it is not computationally more expensive.
Core tip: In meta-analysis of bivariate P value, keeping the inherent paired structure and thus reserving the correlation between the each member of the paired P-values is critical. In this work, we propose a novel meta-analysis technique which does keep this paired structure intact and thus results in much more favorable sensitivity and specificity characteristics compared to the existing method by George and Mudholkar’ (1983), which treats the P value as independent.