Haplomap

Haplotype-based computational genetic mapping (a.k.a HBCGM)

Haplomap is a successor project of HBCGM, as development on the latter was last continued in 2010. Haplomap has been adopted as a replacement for the original HBCGM

Citation:

Zhuoqing Fang, Gary Peltz, An Automated Multi-Modal Graph-Based Pipeline for Mouse Genetic Discovery, Bioinformatics, 2022;, btac356, https://doi.org/10.1093/bioinformatics/btac356

see what's new in the CHANGELOG.

Dependency

Works both on Linux and MacOS

Haplomap:

• CMake
• GCC >= 4.8
• clang >= 11.0.3 (only tested with 11.x version)
• C++11
• GSL

For Variant Calling, you need:

• GATK 4.x
• SAMtools
• BCFtools
• BEDtools
• BWA

Running pipeline

• Snakemake

Installation

conda install -c bioconda haplomap

Installl from source

1. Install GSL first e.g.

Ubuntu

sudo apt-get install libgsl-dev

MacOS

brew install gsl

or compile GSL(makesure that GSL include and lib path is exported)

./configure --prefix=${HOME}/program/gsl
make && make install
# you may need to add this line to your .bashrc 
export LD_LIBRARY_PATH="${HOME}/program/gsl/lib:$LD_LIBRARY_PATH"

2. build and install to path

cd ${haplomap_repo}
mkdir build && cd build
cmake -DCMAKE_BUILD_TYPE=Release -DCMAKE_INSTALL_PREFIX=/path/to/directory/bin ..
make

Usage

Run haplomap standalone

See more detail in haplomap subfolder: Run haplomap standalone

Use snakemake workflow to run Mouse Phenome Database (MPD) datasets

0. Variant calling

See variant calling using GATK, BCFtools, svtools.

e.g.

# modify the file path in haplomap and run with 12 cores
snakemake -s workflows/bcftools.call.smk  --configfile config.yaml \
          -k -p -j 12   

Mouse Phenome Database have > 10K datasets. Try to configure the files below to run

1. Prepare MPD measnum id file. One id per row, suffixed with "-m" or "-f"(f: female, m: male)

26720-m
26720-f
9940-f
...

2. Edit the config.yaml file path in workflows folder:

only edit HBCGM section.

HBCGM:
    # working directory
    WORKSPACE: "/data/bases/fangzq/MPD/results_drug_diet"
    # path to haplomap
    BIN: "/home/fangzq/github/HBCGM/build/bin"
    
    # MPD id file, one id per line 
    TRAIT_IDS: "/data/bases/fangzq/MPD/drug-diet.ids.txt"
    # set to true will select individual animal data. Default: use strain means.   
    USE_RAWDATA: false 
    # strains metadata: map strain abbrev to full name, jax ids, etc. 
    # see docs folder to view examples
    STRAIN_ANNO: "/data/bases/shared/haplomap/PELTZ_20210609/strains.metadata.csv"
    
    # filtered VCF files after variant calling step 
    VCF_DIR: "/data/bases/shared/haplomap/PELTZ_20210609/VCFs"
    # Ensembl-vep output after variant calling step
    VEP_DIR: "/data/bases/shared/haplomap/PELTZ_20210609/VEP"

    ## Optional files
    # genetic relation file from PLink output
    GENETIC_REL: "/data/bases/shared/haplomap/PELTZ_20210609/mouse54_grm.rel"
    # gene expression file 
    GENE_EXPRS: "/data/bases/shared/haplomap/PELTZ_20210609/mus.compact.exprs.txt"

3. run haplomap pipeline

3.1 create conda envs

conda create -n hbcgm -f environment.yaml

3.2 run on a local computing node.

source activate hbcgm
# modify the file path in haplomap and run with 24 cores
snakemake -s workflows/haplomap.smk \
          --configfile workflows/config.yaml 
          -k -p -j 24   

3.3 Run on the HPC, e.g. Stanford Sherlock

e.g. Sherlock slurm

1. edit slurm.submit.sh, change file path to HBCGM/workflows
2. edit workflows/slurm_config.yaml, specify the resource you need.
3. submit

sbatch slurm.submit.sh

Output

output explanation, see here: Run haplomap standalone

Contact

Email:

• Zhuoqing Fang: fangzq@stanford.edu
• Gary Peltz: gpeltz@stanford.edu

Copyright and License Information

Copyright (C) 2019-2022 Stanford University, Zhuoqing Fang and Gary Peltz.

Authors: Zhuoqing Fang and Gary Peltz.

The original HBCGM (the maximal haplotype construction method) was developed by Dr. David Dill and Dr. Gary Peltz at Stanford.

HBCGM/Halomap is patented to Dr. Gary Peltz.

This program is licensed with commercial restriction use license. Please see the attached LICENSE file for details.