esohkevin / hapbin

Efficient program for calculating Extended Haplotype Homozygosity (EHH) and Integrated Haplotype Score (iHS)

hapbin

hapbin is a collection of tools for efficiently calculating Extended Haplotype Homozygosity (EHH), the Integrated Haplotype Score (iHS) and the Cross Population Extended Haplotype Homozogysity (XP-EHH) statistic.

Tools

The hapbin suite contains the following tools:

• ehhbin --hap [.hap/.hapbin file] --map [.map file] --locus [locus] --out [output prefix] - calculate the EHH
• ihsbin --hap [.hap/.hapbin file] --map [.map file] --out [output prefix] - calculate the iHS of all loci in a .hap/.hapbin file
• xpehhbin --hapA [Population A .hap/.hapbin] --hapB [Population B .hap/.hapbin] --map [.map file] --out [output prefix] - calculate the XPEHH of all loci in .hap/.hapbin files.
• hapbinconv --hap [.hap ASCII file] --out [.hapbin binary file] - convert .hap file to more size efficient binary format.

For additional options, see [executable] --help.

Copyright and License

This code is licensed under the GPL v3. Copyright is retained by the original authors, Colin Maclean and the University of Edinburgh.

Citation

Maclean CA, Chue Hong NP, Prendergast JG. hapbin: An Efficient Program for Performing Haplotype-Based Scans for Positive Selection in Large Genomic Datasets. Mol Biol Evol. 2015 Nov;32(11):3027-9. doi: 10.1093/molbev/msv172

Building from source code

Dependencies

• A C++11 capable compiler (GCC >= 4.7 for required features). OpenMP support required for threaded execution.

• Optional dependency: MPI for execution on distributed memory systems (clusters/supercomputers).

If any of these are not already installed on your system then for the main Linux distributions they can simply be added via their package managers.

For example to install on Ubuntu (tested on 14.04 LTS):

 sudo apt-get update
 sudo apt-get install git cmake libcr-dev mpich libmpich-dev

On openSUSE (tested on Enterprise Server 12):

 sudo zypper install cmake git-core gcc-c++ openmpi openmpi-devel
 export PATH=$PATH:/usr/lib64/mpi/gcc/openmpi/lib64:/usr/lib64/mpi/gcc/openmpi/bin

On Red Hat (tested on Enterprise Linux 7.1):

 sudo yum install cmake git gcc-c++

For those servers where CMake is not installed, and you do not have the necessary permissions to add it as above, precompiled binaries can be downloaded from here.

Building the source code

An out of source build is suggested in order to keep the source directory clean. To do this, check out the hapbin source, move to the build directory, then run cmake [path to src directory]. Once CMake has finished generating the necessary files, simply run make.

For example:

 git clone https://github.com/evotools/hapbin.git
 cd hapbin/build/
 cmake ../src/
 make

Installing with an alternate toolchain

First, check out the hapbin source:

git clone https://github.com/evotools/hapbin.git
cd hapbin/build/

Next, create a toolchain.cmake file with the necessary overrides:

...
SET(CMAKE_C_COMPILER "/path/to/c/compiler")
SET(CMAKE_CXX_COMPILER "/path/to/cxx/compiler")
...

MPI_C_LIBRARIES, MPI_CXX_LIBRARIES, MPI_C_INCLUDE_PATH, and MPI_CXX_INCLUDE_PATH can be set in this file, too, if necessary.

Then, tell cmake to use this toolchain and build:

cmake ../src/ -DCMAKE_TOOLCHAIN_FILE=toolchain.cmake
make

Installing on ARCHER

If you are using hapbin on the ARCHER UK National HPC Service, follow these steps:

1. Download hapbin: git clone https://github.com/evotools/hapbin.git

2. Navigate to the build directory: cd hapbin/build

3. Run . build.archer.sh or source build.archer.sh to load/switch required environment modules and configure/install hapbin.

4. Install to /work/[project code]/[group code]/[username]/hapbin/ by typing make install

5. Copy desired hapbin.[haps].[threads].pbs from hapbin/tools/pbs/hapbin to /work/[project code]/[group code]/[username]/hapbin/bin/

6. cd /work/[project code]/[group code]/[username]/hapbin/bin, edit PBS as desired, and submit to the batch queue with qsub.

Input file formats

The hap files (--hap), containing phased haplotypes, should be in IMPUTE hap format. These can be optionally converted to smaller binary files for use with the hapbin suite of tools using hapbinconv. IMPUTE provides phased haplotypes in this format for several publically available human cohorts here. If your data is in VCF format it can be converted to IMPUTE format using vcftools. See the FAQ below for more details.

The map files (--map) should be in the same format as used by Selscan with one row per variant and four space-separated columns specifiying chromosome, locus ID, genetic position and physical position.

Output file formats

• ehhbin outputs five columns. The first three being the locus' ID and its genetic and physical positions. These are followed by two columns corresponding to the EHH for each of the alleles at this locus (allele coded as 0 then 1).
• ihsbin outputs a file with each allele's iHH value (iHH_0 and iHH_1) as well as the unstandardised and standardised iHS values (alleles grouped in to 2% frequency bins for standardisation by default). The first column is the zero-indexed location of the SNP in the hap and map files. The second column is the SNP's locus id (as specified in the map file).
• xpehh outputs a file containing six columns: the zero-indexed location, the SNP locus id (as specified in the map file), corresponding iHH values, and finally the XP-EHH value.

Examples

Example command for calculating EHH for a variant with ID (--locus) of 140465 as specified in the map input file. Output is redirected to a file named 140465_EHH.txt:

 ./ehhbin --hap 1000GP_Phase3.GBR.chr22.hap --map chr22.map --locus 140465 > 140465_EHH.txt

Example command for calculating the iHS of all variants with a minor allele frequency greater than 10% (--minmaf 0.1) and specifying that the integral of the observed decay of EHH (i.e. iHH, see Voight et al. for more information) should be calculated up to the point at which EHH drops below 0.1 (--cutoff 0.1):

 ./ihsbin --hap 1000GP_Phase3.GBR.chr22.hap --map chr22.map --out chr22_iHS --minmaf 0.1 --cutoff 0.1

Example command for calculating XP-EHH with default values for minor allele frequency and EHH cutoff:

 ./xpehhbin --hapA 1000GP_Phase3.GBR.chr22.hap --hapB 1000GP_Phase3.YRI.chr22.hap --map chr22.map --out chr22_GBRvsYRI_XPEHH

Each of the input files referred to in these examples can be found in the data directory.

Frequently asked questions

1. Why do selscan and hapbin give me slightly different iHS values with the same input data?

By default selscan calculates homozygosity values using binomial coefficents. Hapbin uses the sum of the squared haplotype frequencies which can also be used by selscan using the --alt flag. When the --alt flag is used with selscan the two approaches should be comparable.

2. Can hapbin take VCF files as input?

Not directly, but it is possible to use vcftools to convert VCF files to IMPUTE format for use with hapbin. For example using the following vcftools command:

  vcftools --gzvcf genotypes.vcf.gz --IMPUTE