== Useful Wiki Pages ==
There are several pages in this Wiki that may be useful to RAREMETAL users. Here are links to key pages:
* The [[RAREMETAL_Change_Log | Change
* The [[RAREMETAL_DOWNLOAD_%26_BUILD | DOWNLOAD page]]
* The [[Tutorial:_RAREMETAL|RAREMETAL Quick Start Tutorial]]
* The [[RAREMETAL FAQ]]
The [http://genome.sph.umich.edu/wiki/Rvtests '''rvtests'''] tool for rare-variant association analysis can also generate output compatible with RAREMETAL.
== Key Features ==
'''RAREMETAL''' has the following features:
* '''RAREMETAL''' performs gene-based or region-based meta analysis using Burden tests with the following methods: CMC_counts, Madsen-Browning, SKAT, and Variable Threshold.
* '''RAREMETAL''' performs single variant metal-analysis by default.
* '''RAREMETAL''' allows customized groups of variants to be tested.
* '''RAREMETAL''' allows conditional analysis to be performed in both gene-level meta-analysis and single variants meta-analysis.
* '''RAREMETAL''' generate QQ plots and manhattan plots by default.
== Brief Description ==
'''RAREMETAL''' is a computationally efficient tool for meta-analysis of rare variants using sequencing or genotyping array data.
'''RAREMETAL''' takes summary statistics and LD matrices generated by [[Rare-Metal-Worker|'''RAREMETALWORKER''']] or [http://genome.sph.umich.edu/wiki/Rvtests '''rvtests'''], handles related and unrelated individuals, and supports both single variant and burden meta-analysis. '''RAREMETAL''' generates high quality plots by default and has options that allow users to build reports at different levels.
'''RAREMETAL''' is developed by Shuang Feng, Dajiang Liu and Gonçalo Abecasis. A R-package written by Dajiang Liu using the same methodology is [[RareMetals|'''available''']].
== Approach ==
== Download and Installation ==
* University of Michigan CSG users can go to the following:
=== Where to Download ===
We have tested compilation using our source code on several platforms including Linux,
MAC OS X , and Windows.
For source code and executables together with instructions of building from source, please go to [[RAREMETAL_DOWNLOAD_%26_BUILD |'''DOWNLOAD source and executables''']].
For questions about compilation, please go to [[RAREMETAL_FAQ | '''FAQ''']].
=== How to Execute ===
* Go to raremetal_0.4.9/raremetal/bin and use the following:
* For example usage, please refer to [[http://genome.sph.umich.edu/wiki/Rare-Metal#Example_Usage example command lines]]
== Basic Usage Instructions ==
* Currently, CMC type burden test, Madsen-Browning burden test, Variable Threshold burden test and SKAT are provided in '''RAREMETAL''', by specifying --burden, --MB, --VT and --SKAT.
* --maf specifies the minor allele frequency cutoff when doing gene-based or group-based burden tests. Variants with maf '''above''' this threshold will be ignored. The default is maf<0.05.
* In a study of sample size N, if a site is monomorphic or not reported in vcf/ped, it is considered that the sample size of this study is not large enough to sample the rare allele. Thus, this study contributes 2*N reference alleles and 0 alternative allele towards meta-analysis. To let such studies contribute no alleles towards pooled allele frequency, specify --altMAF.
==== Conditional Analysis====
Sai Chen ( saichen at umich dot edu) for questions.
== Change Log == * Version 0.0.1 released to U of M CSG group. (2/13/2013) * Version 0.0.1 released. (2/24/2013) * Version 0.1.2 released after fixing a few bugs, adding conditional analysis and automatic graphing to the tool. (8/5/2013) * Version 0.2.9 released after fixing a bug in SKAT and writing PDF when all variants are monomorphic. (10/7/2013) * Version 0.3.1 released to fix a bug when one of the alleles coded as missing. * Version 0.4.0 released with a few bugs fixed to properly handling missing genotypes. Major change in command options. Now allow user to specify list of summary statistics files and covariance files separately using --summaryFiles and --covFiles options. * Version 0.4.2 released with a bug fixed for SKAT when there are two variants in a group, and a bug fixed in Makefile for easy compiling. * Version 0.4.4 released with a bug fixed when alleles are flipped in group file. (3/14/2014) * Merged raremetal and raremetalworker in one package following version number of raremetalworker. Completed testing compiling on various platforms. (4/22/14)