Package: pheval-exomiser
Exomiser Runner for PhEvalThis is the Exomiser plugin for PhEval. With this plugin, you can leverage the variant prioritisation tool, Exomiser, to run the PhEval pipeline seamlessly. Detailed documentation on how to set up and run the PhEval Makefile pipeline with the Exomiser runner can be foundhere. The setup process for running the full PhEval Makefile pipeline differs from setting up for a single run. The Makefile pipeline creates directory structures for corpora and configurations to handle multiple run configurations. Detailed instructions on setting up the appropriate directory layout, including the input directory and test data directory, can be found here.InstallationClone the pheval.exomiser repo and set up the poetry environment:gitclonehttps://github.com/monarch-initiative/pheval.exomiser.gitcdpheval.exomiser
poetryshell
poetryinstallConfiguring asinglerun:Setting up the input directoryAconfig.yamlshould be located in the input directory and formatted like so:tool:exomisertool_version:13.2.0variant_analysis:Truegene_analysis:Truedisease_analysis:Falsetool_specific_configuration_options:environment:localexomiser_software_directory:exomiser-cli-13.2.0analysis_configuration_file:preset-exome-analysis.ymlmax_jobs:0application_properties:remm_version:cadd_version:hg19_data_version:2302hg19_local_frequency_path:# name of hg19 local frequency filehg38_data_version:2302hg38_local_frequency_path:# name of hg38 local frequency filephenotype_data_version:2302cache_type:cache_caffeine_spec:post_process:score_name:combinedScoresort_order:DESCENDINGThe bare minimum fields are filled to give an idea on the requirements. This is so that the application.properties for Exomiser can be correctly configured. An example config has been providedpheval.exomiser/config.yaml.The Exomiser input data directories (phenotype database and variant database) should also be located in the input directory - or a symlink pointing to the location.Theexomiser_software_directorypoints to the name of the Exomiser distribution directory located in the input directory.The analysis configuration file (in this case:preset-exome-analysis.yml) should be located within the input directory.If using optional databases, such as REMM/CADD/local frequency the optional data input should look like so in the input
directory:├── cadd
│   └── {{CADD-VERSION}}
│       ├── hg19
│       │   ├── InDels.tsv.gz
│       │   └── whole_genome_SNVs.tsv.gz
│       └── hg38
│           ├── InDels.tsv.gz
│           └── whole_genome_SNVs.tsv.gz
├── local
│   ├── local_frequency_test_hg19.tsv.gz
│   └── local_frequency_test_hg38.tsv.gz
└── remm
    ├── ReMM.v{{REMM-VERSION}}.hg19.tsv.gz
    └── ReMM.v{{REMM-VERSION}}.hg38.tsv.gzThe overall structure of the input directory should look like this with the cadd, local and remm directories being optional, depending on the exomiser configuration:.
├── 2302_hg19
│   ├── 2302_hg19_clinvar_whitelist.tsv.gz
│   ├── 2302_hg19_clinvar_whitelist.tsv.gz.tbi
│   ├── 2302_hg19_genome.h2.db
│   ├── 2302_hg19_transcripts_ensembl.ser
│   ├── 2302_hg19_transcripts_refseq.ser
│   ├── 2302_hg19_transcripts_ucsc.ser
│   └── 2302_hg19_variants.mv.db
├── 2302_phenotype
│   ├── 2302_phenotype.h2.db
│   ├── hp.obo
│   ├── phenix
│   │   ├── ALL_SOURCES_ALL_FREQUENCIES_genes_to_phenotype.txt
│   │   ├── hp.obo
│   │   └── out
│   └── rw_string_10.mv
├── config.yaml
├── exomiser-cli-13.2.0
│   ├── lib
│   └── exomiser-cli-13.2.0.jar
├── preset-exome-analysis.yml
├── cadd
│   └── {{CADD-VERSION}}
│       ├── hg19
│       │   ├── InDels.tsv.gz
│       │   └── whole_genome_SNVs.tsv.gz
│       └── hg38
│           ├── InDels.tsv.gz
│           └── whole_genome_SNVs.tsv.gz
├── local
│   ├── local_frequency_test_hg19.tsv.gz
│   └── local_frequency_test_hg38.tsv.gz
└── remm
    ├── ReMM.v{{REMM-VERSION}}.hg19.tsv.gz
    └── ReMM.v{{REMM-VERSION}}.hg38.tsv.gzSetting up the testdata directoryThe Exomiser plugin for PhEval accepts phenopackets and vcf files as an input for running Exomiser. The plugin can be run inphenotype_onlymode, where only phenopackets are required as an input, however, thismustbe specified in theconfig.yaml.The testdata directory should include subdirectories namedphenopacketsandvcfif running with variant prioritisation.e.g.,├── testdata_dir
   ├── phenopackets
   └── vcfRun commandOnce the testdata and input directories are correctly configured for the run, thepheval runcommand can be executed.phevalrun--input-dir/path/to/input_dir\--testdata-dir/path/to/testdata_dir\--runnerexomiserphevalrunner\--output-dir/path/to/output_dir\--version13.2.0Common errorsYou may see an error that is related to the currentsetuptoolsbeing used:pkg_resources.extern.packaging.requirements.InvalidRequirement:ExpectedclosingRIGHT_PARENTHESISrequests(<3,>=2.12.*);extra=='parse'~~~~~~~~~~^To fix the error,setuptoolsneeds to be downgraded to version 66:pipuninstallsetuptools
pipinstall-Usetuptools=="66"