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* 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.
== 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 ==
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''']].
== Basic Usage Instructions ==
Files containing summary statistics and LD matrices generated by '''RAREMETALWORKER''' should be compressed and [http://samtools.sourceforge.net/tabix.shtml '''tabix'''] indexed using the following commands (Note in RAREMETALWORKER, if --zip is specified these .gz and .tbi files will be automatically generated):
* The above example study name file guides '''RAREMETAL''' to look for summary statistics from TwinsUK study only, because "HUNT" study is commented out. The following two files are needed for '''RAREMETAL''' to perform further analysis together with their tabix index file are needed.
=====Group Rare Variants=====
* 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====
* The annotated VCF file should be specified using --annotatedVcf option.
* --annotation should be used with --annotatedVcf together when specific category of functional variants are of interest to be grouped. For example, if grouping nonsynonymous and splicing variants are of interests, the following should be included in command line:
--annotatedVcf your.annotated.vcf --annotation nonsyn/splicing
Shuang Feng ( sfengsph at umich dot edu) for questions.