metapro

Introduction

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

1. ordmeta : Minimum marginal p-value in joint order distribution
2. wFisher : weighted Fisher's method
3. wZ : weighted Z-method
4. 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.

Installation

Prerequisites

1. JAVA : If not installed yet, please install it first. Download: https://www.java.com/en/
   
2. 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)

Usage

1. ordmeta

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).

Example

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] "+"

Input Arguments and Values

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.

2. wFisher

wFisher is designed to assign weights to each experiment based on the sample size.

Example

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] "+"

Input Arguments and Values

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.

3. wZ

Weighted Z-method. This function has been modified from sumz function in metap package.

Example

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

Input Arguments and Values

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

4. lancaster

Lancaster's procedure - the generalized version Fisher's method

Example

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] "+"

Input Arguments and Values

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.

Contact

Sora Yoon: ysora90@gmail.com
Department of Biological Sciences, UNIST