Phasing of genotypes obtained by Next Generation Sequencing

Phasing is the inference of haplotype phase from genotypes. The repository provides the scripts to automate the phasing with the use of several tools described in scientific literature.

Tools

Genotype based solutions

• SHAPEIT 4.2.2 is a software package to estimate haplotypes in large genotype datasets obtained by whole genome sequencing and DNA micoarrays (Delaneau et al., 2019).

• Eagle 2.4.1 is a very fast HMM-based algorithm to estimate haplotypes within a genotyped cohort or using a phased reference panel (Loh et al., 2016).

• Beagle 5.4 phases genotypes and impute ungenotyped markers.

Sequence based solutions

• WhatsHap phases genomic variants using DNA sequencing reads. It is a read-based phasing solution. Both bam and vcf files are required to run this program.

• HapCUT2 is a maximum-likelihood-based tool for assembling haplotypes from DNA sequence reads.

Scripts

• phase-01.py is a wrapper script to phase the genotypes given as vcf.gz file by SHAPEIT4 and Eagle2.

# Phase with SHAPEIT
python3 /path/to/phase-01.py -r /path/to/resources.csv /path/to/sample.vcf.gz

where resources.csv is the comma seperated text file with the paths to the programs and files applied and sample.vcf.gz is the original genotypes under VCF file archived with bgzip tool.

# Phase with Eagle
python3 /path/to/phase-01.py -r /path/to/resources.csv --tool eagle /path/to/sample.vcf.gz

• phase-02.py is the wrapper script to phase the genotypes given as vcf.gz file with Beagle 5.4 tool.

# Phase with Beagle 
python3 /path/to/phase-02.py -r /path/to/resources.csv /path/to/sample.vcf.gz

• estimate-switch-error-01.py is the script to estimate the switch error with vcftools for several samples.

python3 estimate-switch-error-01.py path/to/filename.txt path/to/out_folder

where filename.txt is the 3 column space delimited text file. Each row has the paths to first and second vcf.gz files as well as the sample id. out_folder is the folder to save the files created by vcftools.

Third-party datasets

Reference haplotypes

Recombination map

References

Olivier Delaneau, Jean-Francois Zagury, Matthew R Robinson, Jonathan Marchini, Emmanouil Dermitzakis. Accurate, scalable and integrative haplotype estimation. Nat. Comm. 2019.

Loh P-R, Danecek P, Palamara PF, Fuchsberger C, Reshef YA, Finucane HK, Schoenherr S, Forer L, McCarthy S, Abecasis GR, Durbin R, and Price AL. Reference-based phasing using the Haplotype Reference Consortium panel. Nature Genetics, 2016.

Loh P-R, Palamara PF, and Price AL. Fast and accurate long-range phasing in a UK Biobank cohort. Nature Genetics, 2016.