phimtools: A phasing and imputation tools for NGS data.

Introduction

phimtools is a phasing and imputation tools for NGS data, which is the main core of imputation server. You can use phimtools as your own imputation pipeline in your local Linux cluster.

Quick start

phimtools use Eagle or beagle(requires Java version 8) for phasing and Minimac3 or Minimac4 for imputation.

Installation

Install the released version by pip:

pip install phimtools

This command will install phimtools in your system and you can use phimtools in your commandline.

Important notes before starting

We have Eagle_v2.4.1 and beagle_5.2 built in phimtools. However, ensure that Java version 8 (for beagle), and minimac4 (or minimac3) softwares are installed in your analysis environment.

Reference_panel or genetic_map files are necessities and should be download from:

• Eagle (Genetic maps files):　 https://alkesgroup.broadinstitute.org/Eagle/downloads/Eagle_v2.4.1.tar.gz
• beagle:　　　　　　　　　　https://faculty.washington.edu/browning/beagle/beagle.html
  • Genetic maps files:　　　http://bochet.gcc.biostat.washington.edu/beagle/genetic_maps/
  • Reference Panels files:　http://bochet.gcc.biostat.washington.edu/beagle/1000_Genomes_phase3_v5a/
• Minimac3:　　　　　　　　　https://genome.sph.umich.edu/wiki/Minimac3#Download
  • Reference Panels files:　https://genome.sph.umich.edu/wiki/Minimac3#Reference_Panels_for_Download
• Minimac4:　　　　　　　　　https://genome.sph.umich.edu/wiki/Minimac4#Installation
  • install:

  git clone https://github.com/statgen/Minimac4.git
  cd Minimac4
  bash install.sh
  

  • Reference Panels files:　 https://genome.sph.umich.edu/wiki/Minimac4#Reference_Panels_for_Download

Usage

You can find all the submodules for phasing and imputation process by running: phimtools --help:

usage: phimtools {init, impute, eagle, beagle, minimac} [option] ...

Initialization:
    init     Configure the absolute path for third-party softwares.

Pipeline:
    impute   (Recommended) Run phasing and imputation pipeline for NGS data.

Third-party programs:
    eagle    Run eagle independently.
    beagle   Run beagle independently.
    minimac  Run minimac independently (if availabled).

Before running:

Eagle/beagle/minimac softwares must be pre-configured (only needs to be configured once) via:

phimtools init --help:

usage: phimtools init [-h] [-e EAGLE] [-b BEAGLE] [-m MINIMAC]

optional arguments:
  -h, --help            show this help message and exit
  -e EAGLE, --eagle EAGLE
                        Specify the absolute path of the Eagle
  -b BEAGLE, --beagle BEAGLE
                        Specify the absolute path of the beagle
  -m MINIMAC, --minimac MINIMAC
                        Specify the absolute path of the Minimac3/minimac4

or run phimtools init to config the built-in Eagle/beagle/Minimac3 softwares, which are not recommended !

impute pipeline:

Once initialized, recommended phasing-impute pipeline is running:

phimtools impute --help:

usage: phimtools impute [-h] -C CONFIG [-M IMPUTE_METHOD] [-P PHASE_METHOD] -I IN_VCF
                 -O OUT_PREFIX --refpanel-version REFPANEL --reference-build
                 REFBUILD [--unprephase] [--regions chr:start-end]
                 [--nCPU NCPU]

optional arguments:
  -h, --help            show this help message and exit
  -C CONFIG, --conf CONFIG
                        YAML configuration file specifying details information for imputation
  -M IMPUTE_METHOD, --methods IMPUTE_METHOD
                        Tools (minimac, beagle) for imputation. [minimac]
  -P PHASE_METHOD, --prephase-method PHASE_METHOD
                        Tools (eagle, beagle) for pre-phase before imputation. [beagle]
  -I IN_VCF, --input IN_VCF
                        Input one VCF file to analyze. Required
  -O OUT_PREFIX, --outprefix OUT_PREFIX
                        Prefix for output files. Required
  --refpanel-version REFPANEL
                        The version of haplotype data for reference panel. Required
  --reference-build REFBUILD
                        The build version of reference, e.g: GRCh38
  --unprephase          Do not perform pre-phased before the imputation process.
  --regions chr:start-end
                        Skip positions which not in these regions. This parameter could be a list of comma deleimited genome regions(e.g.: chr:start-end,chr:start-end)
  --nCPU NCPU           Number of threads. [1]

Configuration file

phimtools impute needs a configuration file for setting the path of phasing program, imputation program, reference version and reference panel. Here's one of the examples for how to create a configuration file: config.yaml.

Examples

This command would be enough for most of your jobs, --nCPU is for setting the number of threads.

phimtools impute -C config.yaml \
    -I your.vcf.gz \
    -O test_outprefix \
    --refpanel-version 1000G_P3_GRCh37 \
    --reference-build GRCh37 \
    --nCPU 4

What if you just want to preform the imputed process in some specific regions. Here is an example for running phimtools in genome region: 21:38347375-38500731 and 22:17203103-17439826.

phimtools impute -C config.yaml \
    -I your.vcf.gz \
    -O test_outprefix \
    --refpanel-version 1000G_P3_GRCh37 \
    --reference-build GRCh37 \
    --regions  21:38347375-38500731,22:17203103-17439826 \
    --nCPU 4

phimtools will perform pre-phasing automatically before perform the imputation process. But sometimes your input VCF file has been phased already. And you don't want to run it again then you can set --unprephase argument to skip that process.

phimtools impute -C config.yaml \
    -I your.vcf.gz \
    -O test_outprefix \
    --refpanel-version 1000G_P3_GRCh37 \
    --reference-build GRCh37 \
    --unprephase \
    --nCPU 4

third-party softwares: Once initialized, you can run the third-party softwares (Eagle/beagle/minimac) independently by:

phimtools eagle

phimtools beagle

phimtools minimac

Now you can use phimtools as your powerful imputation pipeline, once you have finished the setting.