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https://github.com/immunogenomics/goshifter

GoShifter
https://github.com/immunogenomics/goshifter

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GoShifter

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README 

          
# GoShifter



GoShifter is a method to determine enrichment of annotations in GWAS significant loci. The manual can be found in the GoShifter_manual.pdf file. These files were taken from http://www.broadinstitute.org/mpg/goshifter/, and may have small updates and bugfixes. 



**update June 26th, 2017:** You can input LD files precalculated with ProxyFinder (see below).



# Manual



## Requirements

GoShifter is written for **Python 2.7**. It uses the following modules:

* bisect

* subprocess

* chromtree (provided)

* bx-python

* numpy



Numpy and bx-python can be installed using pip.



## Usage

GoShifter is divided into two scripts: 

1. **goshifter.py**, which tests for enrichment of a provided set of SNPs with one genomic annotation of interest

2. **goshifter.strat.py**, which tests for the significance of an overlap of a provided set of SNPs with annotation A stratifying on secondary, possibly colocalizing annotation B.



## **goshifter.py**

### Input files



**snpmap file** - with mappings for the tested set of SNPs, tab delimited, with columns SNP, Chrom, BP. Chromosome in the format ‘chrN’. Must include header. Example: ```cat GoShifter/test_data/bc.snpmappings.hg19.txt```


SNP	Chrom	BP

rs10069690	chr5	1279790

rs1045485	chr2	202149589

rs3757318	chr6	151914113

rs10941679	chr5	44706498

rs13281615	chr8	128355618

rs2823093	chr21	16520832

rs17530068	chr6	82193109

rs2380205	chr10	5886734

rs3803662	chr16	52586341




**annotation** – mappings of the annotation which will be tested for enrichment with the SNP set. Must be in BED format (gzipped), includes Chrom, Start, End columns (no header required). Chromosome in the format ‘chrN’. Example: ```zcat GoShifter/test_data/UCSF-UBC.Breast_vHMEC.bed.gz```


chrY 128031 128231

chrY 142761 142961

chrY 231491 231691

chrY 231983 232183

chrY 233430 233630

chrY 285237 285437

chrY 296657 296857

chrY 1318260 1318460

chrY 1459641 1459841




**ld files** 

When testing for enrichment GoShifter uses LD information for the set of provided SNPs. There are now two options to input LD information:

* precomputed LD files provided by us

* LD files calculated using ProxyFinder



**Precomputed LD files provided by us**

To obtain this information please download precomputed pairwise SNP LD information from (these files are large!): [Location of LD files](https://www.broadinstitute.org/~slowikow/tgp/pairwise_ld/). These path to these files can be specified using the ```--ld``` command line switch (see below). In these files, each pair of variants should be on a single line, values should be tab-separated, and the files should be indexed with [Tabix](http://www.htslib.org/doc/tabix.html). Also, this program requires Tabix to be in the $PATH. These LD files are headerless.



Format of LD files (chrA\tposA\trsIdA\tposB\trsIdB\tRsquared\tDPrime), e.g.:


chr7	143099133	rs10808026	143103481	rs56402156	0.970556	0.992515




**ProxyFinder LD files**

Another option to specify LD is to generate an LD proxy file using a program such as [ProxyFinder](https://github.com/immunogenomics/harmjan/releases). The path to this file can be specified using the ```--proxies``` command line switch (see below). The output of the ProxyFinder program is slightly different than the above LD files, but has as a benefit that it only includes LD information for the SNPs that are of your interest (so that GoShifter doesn't have to do the same tabix queries over and over again). Also, this allows you to generate LD files for other populations easily. To generate these files, please refer to the [ProxyFinder readme.md](https://github.com/immunogenomics/harmjan/tree/master/ProxyFinder).



Format of proxy LD files (chrA\tposA\trsIdA\tchrB\tposB\trsIdB\tDistance\tRsquared\tDPrime), e.g.:


ChromA	PosA	RsIdA	ChromB	PosB	RsIdB	Distance	RSquared	Dprime

Chr2	202149589	rs1045485	Chr2	202149589	rs1045485	0	0.9999999999999981	0.999999999999999

Chr2	202149589	rs1045485	Chr2	202150914	rs35550815	1325	0.9999999999999981	0.999999999999999




### Command line

Goshifter can be run using a single command line:

```./goshifter.py --snpmap FILE --annotation FILE --permute INT --ld DIR --out FILE [--rsquared NUM --window NUM --min-shift NUM --max-shift NUM --ld-extend NUM --nold]```



**Options:**


Usage:

    ./goshifter.py --snpmap FILE --annotation FILE --permute INT [--ld DIR --proxies FILE] --out FILE [--rsquared NUM --window NUM --min-shift NUM --max-shift NUM --ld-extend NUM --no-ld]



Options:

    -h, --help              Print this message and exit.

    -v, --version           Print the version and exit.



    -s, --snpmap FILE       File with SNP mappings, tab delimited, must include header: SNP, CHR, BP. Chromosomes in format chrN.

    -a, --annotation FILE   File with annotations, bed format. No header.

    -p, --permute INT       Number of permutations.

    -i, --proxies FILE      File with proxy information for snps in --snpmap; takes precedence over --ld

    -l, --ld DIR            Directory with LD files

    

    -r, --rsquared NUM      Include LD SNPs at rsquared >= NUM [default: 0.8]

    -w, --window NUM        Window size to find LD SNPs [default: 5e5]

    -n, --min-shift NUM     Minimum shift [default: False]

    -x, --max-shift NUM     Maximum shift [default: False]

    -e, --ld-extend NUM     Fixed value by which to extend LD boundries [default: False]

    -n, --no-ld             Do not include SNPs in LD [default: False]



    -o, --out FILE          Write output file.




### Example usage:

```./goshifter.py --snpmap test_data/bc.snpmappings.hg19.txt --annotation test_data /UCSF-UBC.Breast_vHMEC.bed.gz --permute 1000 --ld 1kG-beaglerelease3/pairwise_ld/ --out test_data/bc.H3K4me1_vHMEC3```



If you make use of LD files precalculated by ProxyFinder, replace ```--ld 1kG-beaglerelease3/pairwise_ld/``` with ```--proxies /path/to/proxyfinderoutput.txt```



GoShifter will output a message on the screen (and print the P-value corresponding to the significance of an overlap). The following output files will be created: 



***.enrich** – output file with observed and permuted overlap values


nperm nSnpOverlap allSnps enrichment

0 29 68 0.42647

1 17 68 0.25

2 26 68 0.38235

3 25 68 0.36765

4 23 68 0.33824

5 17 68 0.25

6 21 68 0.30882

7 25 68 0.36765

8 17 68 0.25




nperm = 0 is the observed overlap

nSnpOverlap – number of loci where at least one SNP overlaps an annotation

allSnps – total number of tested loci

enrichment – nSnpOverlap/allSnps



Note, P-value is the number of times the “enrichment” is greater or equal to the observed overlap divided by total number of permutations.



***.locusscore** – the likelihood of a locus to overlap an annotation under the null. The smaller the value the more likely a locus overlaps an annotation not by chance. Loci not overlapping any annotation are denoted as “N/A”.


locus overlap score

rs11780156 1 0.609

rs4808801 1 0.996

rs10069690 N/A N/A

rs12493607 1 0.888

rs1045485 N/A N/A

rs204247 1 0.678

rs3757318 N/A N/A

rs2943559 N/A N/A

rs11552449 N/A N/A




***.snpscore** – defines which LD SNPs are overlapping an annotation in the observed data


locus ld_snp overlap

rs11780156 rs11780156 1

rs11780156 rs1016578 0

rs11780156 rs12542202 0

rs11780156 rs11776569 0

rs11780156 rs7836152 0

rs11780156 rs10956414 0

rs11780156 rs67397162 0

rs11780156 rs11778142 1

rs11780156 rs11997192 0




## **goshifter.strat.py**



### Input files:



snpmap – see above

annotation-a – mappings of the primary annotation which will be tested for enrichment with the SNP set. See above for format details for the annotation input file.

annotation-b – mappings of the secondary annotation. Assessment of enrichment for annotation-a will be tested stratifying on this annotation-b. See above for format details for the annotation input file.



### Usage:



```./goshifter.strat.py --snpmap FILE --annotation-a FILE --annotation-b FILE --permute INT --ld DIR --out FILE [--rsquared NUM --window NUM --min-shift NUM --max-shift NUM --ld-extend NUM --no-ld]```



If you make use of LD files precalculated by ProxyFinder, replace ```--ld 1kG-beaglerelease3/pairwise_ld/``` with ```--proxies /path/to/proxyfinderoutput.txt```



### Options

Same options as goshifter.py, with the exception:


-a, --annotation-a	FILE	File with primary annotations, bed format. Gzipped. No header.

-b, --annotation-b	FILE	File with annotation to stratify on, bed format. Gzipped. No header.




## Example usage



```./goshifter.strat.py --snpmap test_data/bc.snpmappings.hg19.txt --annotation-a test_data/UCSFUBC. Breast_vHMEC.bed.gz --annotation-b test_data/UCSFUBC.Breast_Myoepithelial_Cells.bed.gz --permute 1000 --ld 1kG-beaglerelease3/pairwise_ld/ --out test_data/bc.H3K4me1_vHMEC_strat_Myoepithelial_Cells```



This will output a message on the screen (and print the P-value corresponding to the significance of an overlap) and write results to *.enrich (see above for explanation of the format).