MOLGENIS Imputation 2.x

The imputation pipeline consists of five main steps:

1. LiftOver
2. Phasing
3. GenotypeHarmonizer
4. Imputation
5. CreateStats

Step 1, LiftOver

During this step, the genomic assembly of the data is converted from one genomebuild to another. At this moment, there are two LiftOver options:

• hg18 -> hg19
• hg38 -> hg19

Tools used by the LiftOver step:

• LiftOver, version 20161011
• PLINK, version 1.9

Step 2, Phasing

During this step, the haplotype structure of the data is determined.

Tools used by the Phasing step:

• SHAPEIT, v2.r837-static

Step 3, GenotypeHarmonizer

During this step, quality control is performed and the data is aligned to the reference data.

Tools used by the GenotypeHarmonizer step:

• GenotypeHarmonizer, version 1.4.18

Step 4, Imputation

During this step, the data is split into many chunks, in order to impute the data properly.

Tools used by the Imputation step:

• IMPUTE4, version r265

Step 5, CreateStats

During this step, statistics are measured for the imputed data.

Tools used by the Imputation step:

• QCTOOL, version 1.4

Running the imputation pipeline

1) Create a directory for your project

mkdir /groups/${GROUP}/${tmpDir}/generatedscripts/${PROJECT}

2) Copy datasheet.csv to this directory and adjust the file to match your project

cp datasheet.csv /groups/${GROUP}/${tmpDir}/generatedscripts/${PROJECT}/

• study: Name of your project
• rawdata: Location of the input data (should be in .bed, .bim, .fam format per chromosome)
• genomeBuild: The genomebuild of your data
• referenceGenome: The reference genome used for imputation, currently supported: gonl and 1000G
• run: Name of the run (e.g. run01)

3) Copy generate_template.sh to this directory and change the settings to match your project

cp generate_template.sh /groups/${GROUP}/${tmpDir}/generatedscripts/${PROJECT}/

4) Generate your jobs

sh generate_template.sh

Your jobs are generated and can be found here: /groups/${GROUP}/${tmpDir}/projects/${PROJECT}/${RUN}/jobs/

5) Submit your jobs

sh submit.sh

Your results can be found here: /groups/${GROUP}/${tmpDir}/projects/${PROJECT}/${RUN}/results/

NOTE: In case of a crash, the temporary results can be found here: /groups/${GROUP}/${tmpDir}/tmp/${PROJECT}/