Changes

== Basic Usage Instructions ==

== Basic Usage Instructions ==

raeMETAL is a command line tool. It is typically run from a Linux or Unix prompt by invoking the command <code>raremetal</code>. An example is included at the bottom of this page.

'''raeMETAL''' is a command line tool. It is typically run from a Linux or Unix prompt by invoking the command <code>raremetal</code>. An example is included at the bottom of this page.

A detailed [[Tutorial:_RareMETAL|'''TUTORIAL''']] with toy data are also available.

A detailed [[Tutorial:_RareMETAL|'''TUTORIAL''']] with toy data are also available.

==== List of Studies ====

==== List of Studies ====

* --studyName option is crucial for '''Rare Metal''' to work. Ignoring this option will lead to FATAL ERROR and '''Rare Metal''' will stop.  

* --studyName option is crucial for '''rareMETAL''' to work. Ignoring this option will lead to FATAL ERROR and '''rareMETAL''' will stop.  

* The file should contain the path and prefix of the studies you want to include.  

* The file should contain the path and prefix of the studies you want to include.  

* If there is one or more studies that you want to excluded from your list, but want to save some effort of generating a new file, you can put a "#" in front of the line of record. '''Rare Metal''' will automatically exclude that study from meta analysis.

* If there is one or more studies that you want to excluded from your list, but want to save some effort of generating a new file, you can put a "#" in front of the line of record. '''rareMETAL''' will automatically exclude that study from meta analysis.

* An example file is in the following:

* An example file is in the following:

   #/net/fantasia/home/sfengsph/prj/raremetal/raremetal/bin/META/HUNT/RareMetalWorker/HUNT_MI_case.TG

   #/net/fantasia/home/sfengsph/prj/raremetal/raremetal/bin/META/HUNT/RareMetalWorker/HUNT_MI_case.TG

* The above example study name file guides '''Rare Metal''' looking for the following files as input (note that the second study has been opt out from the meta analysis, because of the "#" in front of the line)

* The above example study name file guides '''rareMETAL''' looking for the following files as input (note that the second study has been opt out from the meta analysis, because of the "#" in front of the line)

   /net/fantasia/home/sfengsph/prj/raremetal/raremetal/bin/META/TwinsUK/TwinsUK.TG.singlevar.score.txt

   /net/fantasia/home/sfengsph/prj/raremetal/raremetal/bin/META/TwinsUK/TwinsUK.TG.singlevar.score.txt

===== From an Annotated VCF File =====

===== From an Annotated VCF File =====

* If --groupFile option is not specified, '''Rare Metal''' will look for an annotated vcf file as blue print for variants to group.

* If --groupFile option is not specified, '''rareMETAL''' will look for an annotated vcf file as blue print for variants to group.

* The annotated VCF file should be specified using --annotatedVcf option.  

* 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:

* --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:

===== Generate a VCF File to Annotate Outside of Rare Metal =====

===== Generate a VCF File to Annotate Outside of Rare Metal =====

* --writeVCF allows user to write a VCF file including pooled single variants from all studies. Then users can use their favorite annotation tool to annotate the VCF file. After annotating the VCF file, users can use that file as input for '''Rare Metal''' for further gene-based or region-based meta analysis.

* --writeVCF allows user to write a VCF file including pooled single variants from all studies. Then users can use their favorite annotation tool to annotate the VCF file. After annotating the VCF file, users can use that file as input for '''rareMETAL''' for further gene-based or region-based meta analysis.

* The output vcf file will be name as: yourPrefix.pooled.variants.vcf. An example output vcf file is in the following:

* The output vcf file will be name as: yourPrefix.pooled.variants.vcf. An example output vcf file is in the following:

   #CHROM    POS    ID      REF    ALT    QUAL    FILTER  INFO

   #CHROM    POS    ID      REF    ALT    QUAL    FILTER  INFO

==== QC Options ====

==== QC Options ====

* '''Rare Metal''' allows filtering of variants from individual studies by their HWE pvalue and call rate, which are generated as part of the output from '''Rare Metal Worker'''.

* '''rareMETAL''' allows filtering of variants from individual studies by their HWE pvalue and call rate, which are generated as part of the output from '''rareMetalWorker'''.

* To filter by HWE p-values, --hwe option should be used. The default is 0.0, which means not filtering any of the variants.

* To filter by HWE p-values, --hwe option should be used. The default is 0.0, which means not filtering any of the variants.

* To filter by call rate, --callRate option can be specified. The default is 0.0, which allows no filtering utilized.

* To filter by call rate, --callRate option can be specified. The default is 0.0, which allows no filtering utilized.

==== Association Methods ====

==== Association Methods ====

* Currently, four methods are provided in '''Rare Metal''', CMC type burden test, Madsen-Browning burden test, Variable Threshold burden test, and SKAT.

* Currently, four methods are provided in '''rareMETAL''', CMC type burden test, Madsen-Browning burden test, Variable Threshold burden test, and SKAT.

== Additional Analysis Options ==

== Additional Analysis Options ==