The meta-analysis is conducted to increase the statistical power by combining evidences (e.g., effect sizes and p-values) obtained from multiple experiments. The p-value combination has been widely used for meta-analysis when effect sizes are not available. metapro is a CRAN R package that provides functions for p-value combinations. There are four functions including
- ordmeta : Minimum marginal p-value in joint order distribution
- wFisher : weighted Fisher's method
- wZ : weighted Z-method
- lancaster : Lancaster's procedure
The original Fisher's method and (weighted) Z-method have been commonly used for p-value combination. In particular, the Z-method is effective when a feature is associated with most of the cohorts. However, this attributes is disadvantageous detecting partially associated patterns (e.g., detection of African-specific features in trans-ethnic analysis).Therefore, in this study, we designed the ordmeta and wFisher method that work effectively in those situations. The detailed formulas are described in our paper.
Prerequisites
- JAVA : If not installed yet, please install it first. Download: https://www.java.com/en/
- Rtools (for Windows): Rtools are required for Windows users. Download: https://cran.r-project.org/bin/windows/Rtools/
After all prerequisites are installed, open R and install the metapro package by typing
install.packages('devtools') # install 'devtools'
library(devtools)
install_github('unistbig/metapro', INSTALL_opts=c("--no-multiarch"))
library(metapro) # Load metapro package
library(rSymPy)
sympyStart()
or
install.packages('metapro', INSTALL_opts=c("--no-multiarch"))
library(metapro)
library(rSymPy)
sympyStart()
Tip: Dealing with Errors
In most cases, installation errors come from 1) encoding problem and 2) JAVA environment variable settings.
So, please try followings.
Encoding error
On Windows,
- System locale setting modification: Click Start -> Control panel-> Clock and Region -> Region -> Administrative -> Change system locale... -> set 'Current system locale' as English (United States) and check the box in the below (Beta: Use Unicode UTF-8 for worldwide language support).
- Reboot the PC, and execute Rstudio.
- In the R console, type
Sys.setlocale('LC_ALL','C')
and install the package again.
Error from JAVA setting
Most error will occur with rJAVA. In this case, please
- Check whether both JAVA and R are 64-bit, and
- Set proper environment variable for JAVA_HOME, CLASSPATH, and RPATH.
- Tip: System environment variable can be easily set by using Set.setenv() function in R. For example,
Sys.setenv(JAVA_HOME='C:\\Program Files\\Java\\jdk1.8.0_211")
Sys.setenv(CLASSPATH="C:\\Program Files\\Java\\jdk1.8.0_211\\jre\\lib\\ext")
Sys.setenv(RPATH="C:\\Program Files\\R\\R-3.6.0\\bin\\x64")
If you are Linux or Mac OSX user, type following on terminal and re-open the R console after setting the environment variables.
sudo R CMD javareconf
Next, check whether rJAVA is installed correctly, and try installing metapro again.
install.packages('rJava')
library(rJava)
ordmeta combines p-value based on the minimum marginal p-value in the joint order distribution. In the result, it reports the combined p-value, optimal rank, effective p-value indices, marginal p-value at the optimal rank (MMP), and the direction of combined effect size (for two-tailed test).
ordmeta(p=c(0.01, 0.02, 0.8, 0.25), is.onetail=FALSE, eff.sign = c(1,1,1,-1))
will return
$p
[1] 0.004427233
$optimal_rank
[1] 2
$eff.p.idx
[1] 1 2
$MMP
[1] 0.00059203
$overall.eff.direction
[1] "+"
| Arguments | |
|---|---|
| p | A numeric vector of p-values |
| is.onetail | Logical. If set TRUE, p-values are combined without considering the direction of effect, and vice versa. Default: TRUE. |
| eff.sign | A vector of signs of effects. It works when is.onetail = FALSE |
| Value | |
|---|---|
| p | Combined p-value |
| optimal_rank | The optimal rank where minimum marginal p-value exists. |
| eff.p.idx | Indexes of effective p-values |
| MMP | Minimum marginal p-value |
| overall.eff.direction | The direction of combined effects. |
wFisher is designed to assign weights to each experiment based on the sample size.
wFisher(p=c(0.01, 0.02, 0.8, 0.25), weight = c(200, 500, 100, 80), is.onetail=FALSE, eff.sign = c(1,1,1,-1))
will return
$p
[1] 0.003060523
$overall.eff.direction
[1] "+"
| Arguments | |
|---|---|
| p | A numeric vector of p-values |
| is.onetail | Logical. If set TRUE, p-values are combined without considering the direction of effect, and vice versa. Default: TRUE. |
| weight | A numeric vector of weight or sample size for each experiment. Note! If no weight option is given, the original Fisher method is performed. |
| eff.sign | A vector of signs of effects. It works when is.onetail = FALSE |
| Value | |
|---|---|
| p | Combined p-value |
| overall.eff.direction | The direction of combined effects. |
Weighted Z-method. This function has been modified from sumz function in metap package.
wZ(p=c(0.01, 0.02, 0.8, 0.25), weight = c(200, 500, 100, 80), is.onetail=FALSE, eff.sign = c(1,1,1,-1))
will return
[1] 0.001798156
$overall.eff.direction
[1] "+"
$sumz
[1] 2.911558
| Arguments | |
|---|---|
| p | A numeric vector of p-values |
| is.onetail | Logical. If set TRUE, p-values are combined without considering the direction of effect, and vice versa. Default: TRUE. |
| weight | A numeric vector of weight or sample size for each experiment. Note! If no weight option is given, the Stouffer's method is performed. |
| eff.sign | A vector of signs of effects. It works when is.onetail = FALSE |
| Value | |
|---|---|
| p | Combined p-value |
| overall.eff.direction | The direction of combined effects. |
| sumz | Transformed sum of z-values |
Lancaster's procedure - the generalized version Fisher's method
lancaster(p=c(0.01, 0.02, 0.8, 0.25), weight = c(200, 500, 100, 80), is.onetail=FALSE, eff.sign = c(1,1,1,-1))
will return
$p
[1] 0.005694935
$overall.eff.direction
[1] "+"
| Arguments | |
|---|---|
| p | A numeric vector of p-values |
| is.onetail | Logical. If set TRUE, p-values are combined without considering the direction of effect, and vice versa. Default: TRUE. |
| weight | A numeric vector of weight or sample size for each experiment. Required! |
| eff.sign | A vector of signs of effects. It works when is.onetail = FALSE |
| Value | |
|---|---|
| p | Combined p-value |
| overall.eff.direction | The direction of combined effects. |
Sora Yoon: ysora90@gmail.com
Department of Biological Sciences, UNIST