ekg/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.

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 hapbincov. IMPUTE provides phased haplotypes in this format for several publically available human cohorts here.

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 two columns, the EHH for each allele (0 and 1) at each location.
• ihsbin outputs two files, the first containing unstandardised iHS for allele 0 and the second (with the .std extension) containing the corresponding standardised iHS (alleles grouped in to 2% frequency bins for standardisation by default). Each of these output files contains two columns: the SNP locus id (as specified in the map file) and corresponding iHS value.
• xpehh output file also contains two columns: the SNP locus id (as specified in the map file) and corresponding XP-EHH value.

Examples

Example command for calculating EHH for a variant with ID (--locus) of 9189 as specified in the map input file. Output is redirected to file named 9189_EHH.txt:

 ehhbin --hap phasedHaplotypes_chr22.hap --map chr22.map --locus 9189 > 9189_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 phasedHaplotypes_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 EUR_phasedHaplotypes_chr22.hap --hapB AFR_phasedHaplotypes_chr22.hap --map chr22.map --out chr22_EURvsAFR_XPEHH

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.

Building from source code

Dependencies

• A C++11 capable compiler (GCC >= 4.7 for required features). OpenMP support required for threaded execution. Requires MPIRPC from https://github.com/camaclean/MPIRPC.

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

• Optional dependency: QT 5 for the unit test framework. On Ubuntu, see: https://qt-project.org/wiki/Install_Qt_5_on_Ubuntu.

Building the source code

An out of source build is suggested in order to keep the source directory clean. To do this, create a build directory, then run cmake [path to directory] in the build directory.

For example:

 cd /path/to/hapbin
 cd build
 cmake ../src/

Once CMake has finished generating the necessary files, simply run make.

The test programs are created in a test subdirectory. Run these test programs with -help or see the Qt 5 QTest framework documentation for testing and benchmarking options.

Running ctest or make test will run all test programs.

Installing on Ubuntu

First ensure packages required for obtaining and compiling code are installed as well as mpi packages used for parallelisation if required.

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

Install MPIRPC to chosen directory.

 git clone https://github.com/camaclean/MPIRPC.git
 cd MPIRPC/
 cd build/
 cmake ../src/
 make
 sudo make install

Finally download and compile hapbin.

 cd ../../
 git clone -b master https://github.com/evotools/hapbin.git
 cd hapbin/build/
 cmake ../src/
 make -j 4

Installing on ARCHER

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

1. Install MPIRPC.

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.