LODSEQ

LodSeq performs the genetic linkage analysis across families, by computing lod-scores given a gvcf file and a related tfam pedigree file.

Both singlepoint and multipoint parametric linkage analyses are computed using merlin (Abecasis et al. Nature Genetics 2002).

CITATION

Please cite LodSeq using the following DOI: 10.5281/zenodo.1321178.

PREREQUISITES

• Python >= 3.5
• Conda >= 4.3
• Snakemake >= 3.9.0

INSTALLATION

Download genetic maps from the HapMap project:

$ cd data/inputs/
$ wget -nc ftp://ftp.ncbi.nlm.nih.gov/hapmap/recombination/2011-01_phaseII_B37/genetic_map_HapMapII_GRCh37.tar.gz
$ mkdir genetic_map_HapMapII_GRCh37 \
  && tar -zxf genetic_map_HapMapII_GRCh37.tar.gz -C genetic_map_HapMapII_GRCh37
$ cd ../..

Once the prerequisites have been installed, configure the environment. vcftools, plink and merlin will be installed by conda:

$ conda env create -n lodseq --file environment.yaml

Then, check that the external programs have been properly installed:

$ source activate lodseq
$ which vcftools && vcftools
$ which plink && plink
$ which merlin && merlin
$ source deactivate lodseq

QUICK START

The quick start dataset was arbitrarily modified from this available dataset:

https://github.com/jmchilton/SnpEffect/tree/master/papers/Protocol/data/chr7.vcf.gz

• The pedigree was reduced to 6 individus.
• Some genotypes were modified replacing phased genotypes by unphased genotypes.
• Some records were removed to reduce the final file size.

Activate the environment

$ source activate lodseq

Run the workflow (using 2 threads)

$ mkdir test/
$ snakemake -s Snakefile --configfile config.yaml -j 2

Exit

$ source deactivate lodseq

RESULTS

The lod-score results are output into directory test/.

You can choose a different output directory by changing the value of the field out_dir into config.yaml.

Please compare your results to the expected output files:

$ cd data/outputs/mergeResults/
$ ls -1
    results_multipoint_merged_dominant.txt
    results_multipoint_merged_recessive.txt
    results_singlepoint_merged_dominant.txt
    results_singlepoint_merged_recessive.txt

RESULT EXAMPLE

Parametric singlepoint analysis using a recessive model:

$ less test/runSinglePointMerlin/7/results_singlepoint_chr7_recessive.txt
Parametric Analysis, Model Recessive_Model
=======================================================
  POSITION        LOD      ALPHA       HLOD
   7:16487      0.000      0.000      0.000
   7:16671      0.000      0.000      0.000
   7:16692      0.000      0.000      0.000
   7:16712      0.000      0.000      0.000
   7:16717      0.000      0.000      0.000
   7:16719      0.000      0.000      0.000
   7:16787      0.000      0.000      0.000
   7:16798      0.000      0.000      0.000
   7:16878      0.000      0.000      0.000
   7:17881      0.000      0.000      0.000
   7:18510      0.000      0.000      0.000
   7:19181     -2.575      0.000      0.000

See documentation of merlin for a complete description.

WARNINGS

Loci with bad inheritance or loci with multichar allele variation will have a null lod-score (-0.000 or 0.000).

RUN LODSEQ ON A NEW DATASET

Edit the file config.yaml to change parameters of the workflow.

Description of the fields into config.yaml:

vcf            # input gvcf file (.vcf or .vcf.gz)
tfam           # input pedigree tfam file
dom_model      # dominant model file
rec_model      # recessive model file
genetic_maps   # path of the HapMap genetic maps directory
out_dir        # path of the directory containing LodSeq output files
out_log        # path of a log file
out_prefix     # prefix of output files
lod_threshold  # minimal significant lod-score value, must be greater than 0
threads        # number of threads used by multithread steps
chromosomes    # list of chromosomes to analyze

You can also change the parameters of the recessive and dominant models:

$ less data/inputs/parametric_dominant.model
$ less data/inputs/parametric_recessive.model

The parameters of these models are respectively:

• affection name
• disease allele frequency
• penetrances
• model name

See a complete description and examples on merlin website and here.

LODSEQ PIPELINE

AUTHORS

Edith Le Floch, Centre National de Recherche en Génomique Humaine - CEA, Evry, France, edith.le-floch@cea.fr

Elise Larsonneur, Centre National de Recherche en Génomique Humaine - CEA, Evry, France, elise.larsonneur@cea.fr

CONTACT

For help please contact the authors.

LICENSING

LodSeq is released under the terms of the CeCILL license, a free software license agreement adapted to both international and French legal matters that is fully compatible with the GNU GPL, GNU Affero GPL and/or EUPL license.

For further details see LICENSE file or check out http://www.cecill.info/.