Changes

== Key Features ==

== Key Features ==

'''rareMETAL''' has the following 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 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''' performs single variant metal-analysis by default.  

* '''rareMETAL''' allows customized groups of variants to be tested.

* '''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''' 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.

* '''RAREMETAL''' generate QQ plots and manhattan plots by default.

== Brief Description ==

== 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''']], handles related and unrelated individuals, and supports both single variant and burden meta-analysis. '''rareMETAL''' generated high quality plots by default and has options that allow users to build reports at different levels.

'''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''']], handles related and unrelated individuals, and supports both single variant and burden meta-analysis. '''RAREMETAL''' generated 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 using the same methodology is [[RareMetals|available]]]. Manuscript for this tool is in preparation. Please contact sfengsph at umich dot edu for questions.

'''RAREMETAL''' is developed by Shuang Feng, Dajiang Liu and Gonçalo Abecasis. A R-package using the same methodology is [[RareMetals|available]]]. Manuscript for this tool is in preparation. Please contact sfengsph at umich dot edu for questions.

== Approach ==

== Approach ==

The key idea behind meta-analysis with rareMETAL is that various gene-level test statistics can be reconstructed from single variant score statistics and that, when the linkage disequilibrium relationships between variants are known, the distribution of these gene-level statistics can be derived and used to evaluate signifi-cance. Single variant statistics are calculated using the Cochran-Mantel-Haenszel method. The main formulae are tabulated in the following:

The key idea behind meta-analysis with RAREMETAL is that various gene-level test statistics can be reconstructed from single variant score statistics and that, when the linkage disequilibrium relationships between variants are known, the distribution of these gene-level statistics can be derived and used to evaluate signifi-cance. Single variant statistics are calculated using the Cochran-Mantel-Haenszel method. The main formulae are tabulated in the following:

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