### Install via Homebrew Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Commands to install Exomiser using Homebrew and verify the generated directory structure. ```bash brew install exomiser/tap/exomiser ``` ```bash $ tree ~/.exomiser /home/user/.exomiser ├── application.properties └── data ``` -------------------------------- ### Example Output File Paths Source: https://exomiser.readthedocs.io/en/stable/input_files_and_options.html Shows the default file structure for generated analysis results. ```text exomiser-cli-15.1.0/results/manuel_exomiser.html exomiser-cli-15.1.0/results/manuel_exomiser.json exomiser-cli-15.1.0/results/manuel_exomiser.parquet ``` -------------------------------- ### Exomiser Output File List Source: https://exomiser.readthedocs.io/en/stable/_sources/input_files_and_options.rst.txt Example of the files generated in the results directory after an analysis. ```text exomiser-cli-|version|/results/manuel_exomiser.html exomiser-cli-|version|/results/manuel_exomiser.json exomiser-cli-|version|/results/manuel_exomiser.parquet ``` -------------------------------- ### Java Version Output Example Source: https://exomiser.readthedocs.io/en/stable/installation.html Expected output format when running the Java version check command. ```text openjdk 21.0.6 2025-01-21 OpenJDK Runtime Environment (build 21.0.6+7-Ubuntu-124.04.1) OpenJDK 64-Bit Server VM (build 21.0.6+7-Ubuntu-124.04.1, mixed mode, sharing) ``` -------------------------------- ### Install Exomiser on Linux/macOS Source: https://exomiser.readthedocs.io/en/stable/installation.html Commands to download, extract, and prepare the Exomiser application and data files on Unix-based systems. ```bash # Download the Exomiser program (small, fast) wget https://github.com/exomiser/Exomiser/releases/download/exomiser-cli-15.1.0-distribution.zip # Download the data files (large — allow several hours) # If you only need one genome assembly, download only the relevant file. wget https://g-879a9f.f5dc97.75bc.dn.glob.us/data/2512_phenotype.zip wget https://g-879a9f.f5dc97.75bc.dn.glob.us/data/2512_hg38.zip wget https://g-879a9f.f5dc97.75bc.dn.glob.us/data/2512_hg19.zip # Extract the program unzip exomiser-cli-15.1.0-distribution.zip # Extract the data files into the data subdirectory unzip 2512_*.zip -d exomiser-cli-15.1.0/data # Navigate into the Exomiser folder cd exomiser-cli-15.1.0 ``` -------------------------------- ### Run Test Analysis on Windows Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Navigate to the installation directory and execute the test analysis using the command prompt. ```bash cd exomiser-cli-|version| java -jar exomiser-cli-|version|.jar analyse --analysis examples/test-analysis-exome.yml ``` -------------------------------- ### Exomiser Batch Command File Source: https://exomiser.readthedocs.io/en/stable/_sources/input_files_and_options.rst.txt Example content for a batch file containing multiple analysis commands. ```text #This is an example analysis batch file to be run using the --analysis-batch command # #Each line should specify the path of a single analysis file, either relative to the directory the exomiser #is being run from or the full system path. It will run any combination of exomiser commands listed using -h or --help. # # Original format exomiser analysis containing all the sample and analysis information --analysis test-analysis-exome.yml # New preset exome analysis using a v1 phenopacket to submit the phenotype information and adding/overriding the VCF input --preset exome --sample pfeiffer-phenopacket.yml --vcf Pfeiffer.vcf.gz # Using the default analysis (exome) with a v1 phenopacket containing the phenotype information and adding/overriding the VCF input --sample pfeiffer-phenopacket.yml --vcf Pfeiffer.vcf.gz # Using a user-defined analysis with a v1 phenopacket containing the phenotype information and adding/overriding the VCF input --analysis preset-exome-analysis.yml --sample pfeiffer-phenopacket.yml --vcf Pfeiffer.vcf.gz # Using a user-defined analysis with a v1 phenopacket containing the phenotype information and adding/overriding the VCF input --analysis preset-exome-analysis.yml --sample pfeiffer-phenopacket.yml --vcf Pfeiffer.vcf.gz --output output-options.yml ``` -------------------------------- ### Run Test Analysis Source: https://exomiser.readthedocs.io/en/stable/installation.html Command to execute a test analysis to verify the installation is functioning correctly. ```bash cd exomiser-cli-15.1.0 java -jar exomiser-cli-15.1.0.jar analyse --analysis examples/test-analysis-exome.yml ``` -------------------------------- ### Run from Alternate Directory Source: https://exomiser.readthedocs.io/en/stable/_sources/running.rst.txt Executes Exomiser when the working directory differs from the installation directory, requiring an explicit path to application.properties. ```bash java -Dspring.config.location=/full/path/to/your/exomiser-cli/directory/application.properties \ -jar /full/path/to/your/exomiser-cli/directory/exomiser-cli-|version|.jar analyse \ --sample /full/path/to/your/exomiser-cli/directory/examples/pfeiffer-phenopacket.yml \ --vcf /full/path/to/your/exomiser-cli/directory/examples/Pfeiffer.vcf.gz --assembly hg19 \ --output-directory full/path/to/your/results/directory ``` -------------------------------- ### Exomiser Parquet Result Preview Source: https://exomiser.readthedocs.io/en/stable/_sources/result_interpretation.rst.txt Example of the Parquet output format, which can be inspected using tools like DuckDB. ```text rank variant geneSymbol hgncId ensemblGeneId ncbiGeneId moi pValue geneCombinedScore genePhenotypeScore geneVariantScore variantScore isContributingVariant isWhiteListVariant faile ───────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────── 1 "10-123256215-T-G_AD" "FGFR2" "HGNC:3689" "ENSG00000066468" "2263" "AD" 0.000002 0.97066 0.87752 1.0 1.0 true true [] 2 "6-132203615-G-A_AD" "ENPP1" "HGNC:3356" "ENSG00000197594" "5167" "AD" 0.000162 0.711517 0.62356 1.0 1.0 true true [] 3 "7-76069617-TG-T_AD" "ZP3" "HGNC:13189" "ENSG00000188372" "7784" "AD" 0.001186 0.400489 0.502852 0.995171 0.995171 true false [] 4 "13-110855918-C-G_AD" "COL4A1" "HGNC:2202" "ENSG00000187498" "1282" "AD" 0.049614 0.026842 0.506021 0.985988 0.985988 true false [] ``` -------------------------------- ### Configure Pathogenicity Sources Source: https://exomiser.readthedocs.io/en/stable/_sources/advanced_analysis.rst.txt Example configuration for specifying pathogenicity sources in YAML format. ```yaml pathogenicitySources: [REVEL, MVP, REMM] ``` -------------------------------- ### Parquet Data Preview Source: https://exomiser.readthedocs.io/en/stable/result_interpretation.html Example of the tabular data structure found within the Parquet output. ```text rank variant geneSymbol hgncId ensemblGeneId ncbiGeneId moi pValue geneCombinedScore genePhenotypeScore geneVariantScore variantScore isContributingVariant isWhiteListVariant faile ───────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────── 1 "10-123256215-T-G_AD" "FGFR2" "HGNC:3689" "ENSG00000066468" "2263" "AD" 0.000002 0.97066 0.87752 1.0 1.0 true true [] 2 "6-132203615-G-A_AD" "ENPP1" "HGNC:3356" "ENSG00000197594" "5167" "AD" 0.000162 0.711517 0.62356 1.0 1.0 true true [] 3 "7-76069617-TG-T_AD" "ZP3" "HGNC:13189" "ENSG00000188372" "7784" "AD" 0.001186 0.400489 0.502852 0.995171 0.995171 true false [] 4 "13-110855918-C-G_AD" "COL4A1" "HGNC:2202" "ENSG00000187498" "1282" "AD" 0.049614 0.026842 0.506021 0.985988 0.985988 true false [] ``` -------------------------------- ### Check Java Version Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Verify the installed Java version to ensure it meets the minimum requirement of version 21. ```bash java -version ``` -------------------------------- ### Configure Exomiser via JAVA_TOOL_OPTIONS Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Use the JAVA_TOOL_OPTIONS environment variable to set data paths and versions when using Homebrew installations. ```bash export JAVA_TOOL_OPTIONS="-Dexomiser.data-directory=/full/path/to/exomiser-data -Dexomiser.hg38.data-version=2512" ``` -------------------------------- ### Check Java Version Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Verify the installed Java version to ensure it meets the requirement of Java 21 or higher. ```console $ java -version ``` ```console openjdk 21.0.6 2025-01-21 OpenJDK Runtime Environment (build 21.0.6+7-Ubuntu-124.04.1) OpenJDK 64-Bit Server VM (build 21.0.6+7-Ubuntu-124.04.1, mixed mode, sharing) ``` -------------------------------- ### Full Exomiser Analysis Job Configuration Source: https://exomiser.readthedocs.io/en/stable/advanced_analysis.html A comprehensive example of an Exomiser analysis job file defining modes, frequency sources, pathogenicity sources, and processing steps. ```yaml --- analysisMode: PASS_ONLY inheritanceModes: { AUTOSOMAL_DOMINANT: 0.1, AUTOSOMAL_RECESSIVE_HOM_ALT: 0.1, AUTOSOMAL_RECESSIVE_COMP_HET: 2.0, X_DOMINANT: 0.1, X_RECESSIVE_HOM_ALT: 0.1, X_RECESSIVE_COMP_HET: 2.0, MITOCHONDRIAL: 0.2 } frequencySources: [ THOUSAND_GENOMES, TOPMED, UK10K, ESP_AA, ESP_EA, ESP_ALL, GNOMAD_E_AFR, GNOMAD_E_AMR, # GNOMAD_E_ASJ, GNOMAD_E_EAS, GNOMAD_E_FIN, GNOMAD_E_NFE, GNOMAD_E_OTH, GNOMAD_E_SAS, GNOMAD_G_AFR, GNOMAD_G_AMR, # GNOMAD_G_ASJ, GNOMAD_G_EAS, GNOMAD_G_FIN, GNOMAD_G_NFE, GNOMAD_G_OTH, GNOMAD_G_SAS ] # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP, ALPHA_MISSENSE), CADD, REMM # REMM is trained on non-coding regulatory regions # *WARNING* if you enable CADD or REMM ensure that you have downloaded and installed the CADD/REMM tabix files # and updated their location in the application.properties. Exomiser will not run without this. pathogenicitySources: [ REVEL, MVP, ALPHA_MISSENSE ] #this is the standard exomiser order. steps: [ failedVariantFilter: { }, variantEffectFilter: { remove: [ FIVE_PRIME_UTR_EXON_VARIANT, FIVE_PRIME_UTR_INTRON_VARIANT, THREE_PRIME_UTR_EXON_VARIANT, THREE_PRIME_UTR_INTRON_VARIANT, NON_CODING_TRANSCRIPT_EXON_VARIANT, NON_CODING_TRANSCRIPT_INTRON_VARIANT, CODING_TRANSCRIPT_INTRON_VARIANT, UPSTREAM_GENE_VARIANT, DOWNSTREAM_GENE_VARIANT, INTERGENIC_VARIANT, REGULATORY_REGION_VARIANT ] }, frequencyFilter: { maxFrequency: 2.0 }, pathogenicityFilter: { keepNonPathogenic: true }, inheritanceFilter: { }, omimPrioritiser: { }, hiPhivePrioritiser: { } ] ``` -------------------------------- ### Unsupported Java Version Error Source: https://exomiser.readthedocs.io/en/stable/installation.html Error messages indicating that the installed Java runtime is incompatible with the compiled Exomiser classes. ```text Exception in thread "main" java.lang.UnsupportedClassVersionError: org/monarchinitiative/exomiser/cli/Main : Unsupported major.minor version ``` ```text Error: A JNI error has occurred, please check your installation and try again Exception in thread "main" java.lang.UnsupportedClassVersionError: org/monarchinitiative/exomiser/cli/Main has been compiled by a more recent version of the Java Runtime (class file version 55.0), this version of the Java Runtime only recognizes class file versions up to 52.0 ``` -------------------------------- ### Display Exomiser Help Source: https://exomiser.readthedocs.io/en/stable/_sources/running.rst.txt Use this command to view available CLI options and help documentation. ```bash java -jar exomiser-cli-|version|.jar --help ``` -------------------------------- ### Exomiser VCF INFO Field Definition and Example Data Source: https://exomiser.readthedocs.io/en/stable/result_interpretation.html The INFO field contains pipe-separated values for compatible modes of inheritance. This example shows the header definition and sample variant records. ```text ##INFO= #CHROM POS ID REF ALT QUAL FILTER INFO sample 10 123256215 . T G 100 PASS Exomiser={1|10-123256215-T-G_AD|FGFR2|2263|AD|0.0000|0.9981|1.0000|1.0000|1.0000|1|1|missense_variant|FGFR2:ENST00000346997.2:c.1688A>C:p.(Glu563Ala)|LIKELY_PATHOGENIC|PM2&PP3_Strong&PP4&PP5|OMIM:123150|"Jackson-Weiss syndrome"};GENE=FGFR2;INHERITANCE=AD;MIM=101600 GT:DS:PL 1|0:2.000:50,11,0 11 1018088 . TG T 441.81 PASS AC=1;AF=0.50;AN=2;BaseQRankSum=7.677;DP=162;DS;Exomiser={7|11-1018088-TG-T_AD|MUC6|4588|AD|0.0096|0.7532|0.5030|0.9990|0.9990|1|0|frameshift_variant|MUC6:ENST00000421673.2:c.4712del:p.(Pro1571Hisfs*21)|UNCERTAIN_SIGNIFICANCE|||""},{8|11-1018088-TG-T_AR|MUC6|4588|AR|0.0096|0.7531|0.5030|0.9990|0.9990|1|0|frameshift_variant|MUC6:ENST00000421673.2:c.4712del:p.(Pro1571Hisfs*21)|UNCERTAIN_SIGNIFICANCE|||""};FS=25.935;HRun=3;HaplotypeScore=1327.2952;MQ=43.58;MQ0=6;MQRankSum=-5.112;QD=2.31;ReadPosRankSum=2.472;set=variant GT:AD:DP:GQ:PL 0/1:146,45:162:99:481,0,5488 11 1018093 . G GT 592.45 PASS AC=1;AF=0.50;AN=2;BaseQRankSum=8.019;DP=157;Exomiser={7|11-1018093-G-GT_AD|MUC6|4588|AD|0.0096|0.7532|0.5030|0.9990|0.9989|0|0|frameshift_elongation|MUC6:ENST00000421673.2:c.4707dup:p.(Pro1570Thrfs*136)|NOT_AVAILABLE|||""},{8|11-1018093-G-GT_AR|MUC6|4588|AR|0.0096|0.7531|0.5030|0.9990|0.9989|1|0|frameshift_elongation|MUC6:ENST00000421673.2:c.4707dup:p.(Pro1570Thrfs*136)|UNCERTAIN_SIGNIFICANCE|||""};FS=28.574;HRun=1;HaplotypeScore=1267.6968;MQ=44.06;MQ0=4;MQRankSum=-5.166;QD=3.26;ReadPosRankSum=1.328;set=variant GT:AD:DP:GQ:PL 0/1:140,42:157:99:631,0,4411 6 132203615 . G A 922.98 PASS AC=1;AF=0.50;AN=2;BaseQRankSum=-0.671;DP=94;Dels=0.00;Exomiser={2|6-132203615-G-A_AD|ENPP1|5167|AD|0.0049|0.8690|0.5773|0.9996|0.9996|1|0|splice_donor_variant|ENPP1:ENST00000360971.2:c.2230+1G>A:p.?|UNCERTAIN_SIGNIFICANCE|PVS1_Strong|OMIM:615522|"Cole disease"};FS=0.805;HRun=0;HaplotypeScore=3.5646;MQ=56.63;MQ0=0;MQRankSum=1.807;QD=9.82;ReadPosRankSum=-0.900;set=variant2 GT:AD:DP:GQ:PL 0/1:53,41:94:99:953,0,1075 ``` -------------------------------- ### Exomiser TSV Result Format Source: https://exomiser.readthedocs.io/en/stable/_sources/result_interpretation.rst.txt Example of the tab-separated values format used for Exomiser results. ```text #RANK ID GENE_SYMBOL ENTREZ_GENE_ID MOI P-VALUE EXOMISER_GENE_COMBINED_SCORE EXOMISER_GENE_PHENO_SCORE EXOMISER_GENE_VARIANT_SCORE EXOMISER_VARIANT_SCORE CONTRIBUTING_VARIANT WHITELIST_VARIANT VCF_ID RS_ID CONTIG START END REF ALT CHANGE_LENGTH QUAL FILTER GENOTYPE FUNCTIONAL_CLASS HGVS EXOMISER_ACMG_CLASSIFICATION EXOMISER_ACMG_EVIDENCE EXOMISER_ACMG_DISEASE_ID EXOMISER_ACMG_DISEASE_NAME CLINVAR_VARIANT_ID CLINVAR_PRIMARY_INTERPRETATION CLINVAR_STAR_RATING GENE_CONSTRAINT_LOEUF GENE_CONSTRAINT_LOEUF_LOWER GENE_CONSTRAINT_LOEUF_UPPER MAX_FREQ_SOURCE MAX_FREQ ALL_FREQ MAX_PATH_SOURCE MAX_PATH ALL_PATH 1 10-123256215-T-G_AD FGFR2 2263 AD 0.0000 0.9981 1.0000 1.0000 1.0000 1 1 rs121918506 10 123256215 123256215 T G 0 100.0000 PASS 1|0 missense_variant FGFR2:ENST00000346997.2:c.1688A>C:p.(Glu563Ala) LIKELY_PATHOGENIC PM2,PP3_Strong,PP4,PP5 OMIM:123150 Jackson-Weiss syndrome 28333 LIKELY_PATHOGENIC 1 0.13692 0.074 0.27 REVEL 0.965 REVEL=0.965,MVP=0.9517972 2 6-132203615-G-A_AD ENPP1 5167 AD 0.0049 0.8690 0.5773 0.9996 0.9996 1 0 rs770775549 6 132203615 132203615 G A 0 922.9800 PASS 0/1 splice_donor_variant ENPP1:ENST00000360971.2:c.2230+1G>A:p.? UNCERTAIN_SIGNIFICANCE PVS1_Strong OMIM:615522 Cole disease NOT_PROVIDED 0 0.41042 0.292 0.586 GNOMAD_E_SAS 0.0032486517 TOPMED=7.556E-4,EXAC_NON_FINNISH_EUROPEAN=0.0014985314,GNOMAD_E_NFE=0.0017907989,GNOMAD_E_SAS=0.0032486517 // 7 11-1018088-TG-T_AD MUC6 4588 AD 0.0096 0.7532 0.5030 0.9990 0.9990 1 0 rs765231061 11 1018088 1018089 TG T -1 441.8100 PASS 0/1 frameshift_variant MUC6:ENST00000421673.2:c.4712del:p.(Pro1571Hisfs*21) UNCERTAIN_SIGNIFICANCE NOT_PROVIDED 0 0.79622 0.656 0.971 GNOMAD_G_NFE 0.0070363074 GNOMAD_E_AMR=0.0030803352,GNOMAD_G_NFE=0.0070363074 7 11-1018093-G-GT_AD MUC6 4588 AD 0.0096 0.7532 0.5030 0.9990 0.9989 0 0 rs376177791 11 1018093 1018093 G GT 1 592.4500 PASS 0/1 frameshift_elongation MUC6:ENST00000421673.2:c.4707dup:p.(Pro1570Thrfs*136) NOT_AVAILABLE NOT_PROVIDED 0 0.79622 0.656 0.971 GNOMAD_G_NFE 0.007835763 GNOMAD_G_NFE=0.007835763 8 11-1018088-TG-T_AR MUC6 4588 AR 0.0096 0.7531 0.5030 0.9990 0.9990 1 0 rs765231061 11 1018088 1018089 TG T -1 441.8100 PASS 0/1 frameshift_variant MUC6:ENST00000421673.2:c.4712del:p.(Pro1571Hisfs*21) UNCERTAIN_SIGNIFICANCE NOT_PROVIDED 0 0.79622 0.656 0.971 GNOMAD_G_NFE 0.0070363074 GNOMAD_E_AMR=0.0030803352,GNOMAD_G_NFE=0.0070363074 8 11-1018093-G-GT_AR MUC6 4588 AR 0.0096 0.7531 0.5030 0.9990 0.9989 1 0 rs376177791 11 1018093 1018093 G GT 1 592.4500 PASS 0/1 frameshift_elongation MUC6:ENST00000421673.2:c.4707dup:p.(Pro1570Thrfs*136) UNCERTAIN_SIGNIFICANCE NOT_PROVIDED 0 0.79622 0.656 0.971 GNOMAD_G_NFE 0.007835763 GNOMAD_G_NFE=0.007835763 ``` -------------------------------- ### Run Exomiser analysis with a Phenopacket Source: https://exomiser.readthedocs.io/en/stable/input_files_and_options.html Basic command to initiate an analysis using a Phenopacket file. ```bash java -jar exomiser-cli-15.1.0.jar analyse --sample examples/pfeiffer-phenopacket.yml ``` -------------------------------- ### Download Exomiser Program Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Use wget to download the Exomiser distribution zip file on Linux or macOS. ```bash # Download the Exomiser program (small, fast) wget https://github.com/exomiser/Exomiser/releases/download/exomiser-cli-|version|-distribution.zip ``` -------------------------------- ### Check Unzip Version Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Verify if the installed unzip utility supports large files by checking for ZIP64_SUPPORT. ```bash unzip -version ``` -------------------------------- ### Run Exomiser with Custom Output Options Source: https://exomiser.readthedocs.io/en/stable/input_files_and_options.html Executes an analysis while applying a custom output configuration file. ```bash java -jar exomiser-cli-15.1.0.jar analyse --sample examples/pfeiffer-phenopacket.yml --vcf path/to/manuel.vcf.gz --output path/to/output-options.yml ``` -------------------------------- ### Run Exomiser Analysis with Sample and VCF Source: https://exomiser.readthedocs.io/en/stable/input_files_and_options.html Executes an analysis by providing a phenopacket sample and a VCF file with a specified genome assembly. ```bash java -jar exomiser-cli-15.1.0.jar analyse --sample examples/pfeiffer-phenopacket.yml --vcf path/to/manuel.vcf.gz --assembly hg19 ``` -------------------------------- ### Define Data Directory Path Source: https://exomiser.readthedocs.io/en/stable/installation.html The target directory for extracted data files within the Exomiser installation folder. ```text exomiser-cli-15.1.0/data ``` -------------------------------- ### Configure Exomiser via Environment Variables Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Set specific environment variables that correspond to properties in the application.properties file. ```bash export EXOMISER_DATA_DIRECTORY=/full/path/to/exomiser-data export EXOMISER_HG38_DATA_VERSION=2602 ``` -------------------------------- ### Run Analysis with VCF and Assembly Source: https://exomiser.readthedocs.io/en/stable/_sources/input_files_and_options.rst.txt Execute an analysis specifying a phenopacket sample, VCF file, and genome assembly. ```bash java -jar exomiser-cli-|version|.jar analyse --sample examples/pfeiffer-phenopacket.yml --vcf path/to/manuel.vcf.gz --assembly hg19 ``` -------------------------------- ### Configure Data Directory Path Source: https://exomiser.readthedocs.io/en/stable/installation.html Sets the base path for Exomiser data files within the application.properties configuration file. ```properties exomiser.data-directory=/data/exomiser-data ``` -------------------------------- ### Run Exomiser Analysis Source: https://exomiser.readthedocs.io/en/stable/_sources/input_files_and_options.rst.txt Execute a standard Exomiser analysis using a YAML configuration file. ```bash java -jar exomiser-cli-|version|.jar analyse --analysis examples/test-analysis-exome.yml ``` -------------------------------- ### Configure Exomiser Output Options Source: https://exomiser.readthedocs.io/en/stable/_sources/input_files_and_options.rst.txt YAML configuration for controlling output directory, file naming, and formats. ```yaml --- outputContributingVariantsOnly: false # numGenes options: 0 = all or specify a limit e.g. 500 for the first 500 results numGenes: 10 minExomiserGeneScore: 0.7 # outputDirectory: (optional) (default: '{exomiserDir}/results/') outputDirectory: results/ # outputFileName: (optional) (default: 'input-vcf-name-exomiser') outputFileName: NA12345-exomiser-results # out-format options: HTML, JSON, PARQUET, TSV_GENE, TSV_VARIANT, VCF (default: HTML) outputFormats: [HTML, PARQUET] ``` -------------------------------- ### VCF INFO Field Structure Source: https://exomiser.readthedocs.io/en/stable/_sources/result_interpretation.rst.txt Example of the Exomiser INFO field format within a VCF file, showing pipe-separated values for ranked alleles. ```text ##INFO= #CHROM POS ID REF ALT QUAL FILTER INFO sample 10 123256215 . T G 100 PASS Exomiser={1|10-123256215-T-G_AD|FGFR2|2263|AD|0.0000|0.9981|1.0000|1.0000|1.0000|1|1|missense_variant|FGFR2:ENST00000346997.2:c.1688A>C:p.(Glu563Ala)|LIKELY_PATHOGENIC|PM2&PP3_Strong&PP4&PP5|OMIM:123150|"Jackson-Weiss syndrome"};GENE=FGFR2;INHERITANCE=AD;MIM=101600 GT:DS:PL 1|0:2.000:50,11,0 11 1018088 . TG T 441.81 PASS AC=1;AF=0.50;AN=2;BaseQRankSum=7.677;DP=162;DS;Exomiser={7|11-1018088-TG-T_AD|MUC6|4588|AD|0.0096|0.7532|0.5030|0.9990|0.9990|1|0|frameshift_variant|MUC6:ENST00000421673.2:c.4712del:p.(Pro1571Hisfs*21)|UNCERTAIN_SIGNIFICANCE|||""},{8|11-1018088-TG-T_AR|MUC6|4588|AR|0.0096|0.7531|0.5030|0.9990|0.9990|1|0|frameshift_variant|MUC6:ENST00000421673.2:c.4712del:p.(Pro1571Hisfs*21)|UNCERTAIN_SIGNIFICANCE|||""};FS=25.935;HRun=3;HaplotypeScore=1327.2952;MQ=43.58;MQ0=6;MQRankSum=-5.112;QD=2.31;ReadPosRankSum=2.472;set=variant GT:AD:DP:GQ:PL 0/1:146,45:162:99:481,0,5488 11 1018093 . G GT 592.45 PASS AC=1;AF=0.50;AN=2;BaseQRankSum=8.019;DP=157;Exomiser={7|11-1018093-G-GT_AD|MUC6|4588|AD|0.0096|0.7532|0.5030|0.9990|0.9989|0|0|frameshift_elongation|MUC6:ENST00000421673.2:c.4707dup:p.(Pro1570Thrfs*136)|NOT_AVAILABLE|||""},{8|11-1018093-G-GT_AR|MUC6|4588|AR|0.0096|0.7531|0.5030|0.9990|0.9989|1|0|frameshift_elongation|MUC6:ENST00000421673.2:c.4707dup:p.(Pro1570Thrfs*136)|UNCERTAIN_SIGNIFICANCE|||""};FS=28.574;HRun=1;HaplotypeScore=1267.6968;MQ=44.06;MQ0=4;MQRankSum=-5.166;QD=3.26;ReadPosRankSum=1.328;set=variant GT:AD:DP:GQ:PL 0/1:140,42:157:99:631,0,4411 6 132203615 . G A 922.98 PASS AC=1;AF=0.50;AN=2;BaseQRankSum=-0.671;DP=94;Dels=0.00;Exomiser={2|6-132203615-G-A_AD|ENPP1|5167|AD|0.0049|0.8690|0.5773|0.9996|0.9996|1|0|splice_donor_variant|ENPP1:ENST00000360971.2:c.2230+1G>A:p.?|UNCERTAIN_SIGNIFICANCE|PVS1_Strong|OMIM:615522|"Cole disease"};FS=0.805;HRun=0;HaplotypeScore=3.5646;MQ=56.63;MQ0=0;MQRankSum=1.807;QD=9.82;ReadPosRankSum=-0.900;set=variant2 GT:AD:DP:GQ:PL 0/1:53,41:94:99:953,0,1075 ``` -------------------------------- ### Run Analysis with Custom Output Options Source: https://exomiser.readthedocs.io/en/stable/_sources/input_files_and_options.rst.txt Execute an analysis while applying a custom output configuration file. ```bash java -jar exomiser-cli-|version|.jar analyse --sample examples/pfeiffer-phenopacket.yml --vcf path/to/manuel.vcf.gz --output path/to/output-options.yml ``` -------------------------------- ### Exomiser Home Directory Structure Source: https://exomiser.readthedocs.io/en/stable/installation.html Displays the directory structure created in the user's home directory upon the first execution of Exomiser. ```text $ tree ~/.exomiser /home/user/.exomiser ├── application.properties └── data ``` -------------------------------- ### Example ACMG variant report format Source: https://exomiser.readthedocs.io/en/stable/_sources/acmg_assignment.rst.txt Shows the structure of an ACMG assignment report for a variant, including the transcript, classification, criteria, and associated disease. ```text 1-12335-A-T, NC_000001.10:g.12335A>T, GENE1(ENST12345678):c.2346A>T:p.1234A>-, PATHOGENIC, [PVS1, PS1, PP4_Strong], Disease (OMIM:12345), AUTOSOMAL_DOMINANT ``` -------------------------------- ### Structural Variant Gene Association Example Source: https://exomiser.readthedocs.io/en/stable/_sources/sv_prioritisation.rst.txt Illustrates how a single structural variant overlapping multiple genes is reported for each gene with its specific predicted effect. ```yaml GENE1: variants: - 1-23456-78910-N- variantEffect: TRANSCRIPT_ABLATION GENE2: variants: - 1-23456-78910-N- variantEffect: EXON_LOSS_VARIANT ``` -------------------------------- ### Enable CADD in application.properties Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Configure the CADD version and file paths in the application.properties file. ```text cadd.version=1.4 exomiser.hg19.cadd-snv-path=${exomiser.data-directory}/cadd/${cadd.version}/hg19/whole_genome_SNVs.tsv.gz exomiser.hg19.cadd-in-del-path=${exomiser.data-directory}/cadd/${cadd.version}/hg19/gnomad.genomes-exomes.r4.0.indel.tsv.gz # and/or for hg38: exomiser.hg38.cadd-snv-path=${exomiser.data-directory}/cadd/${cadd.version}/whole_genome_SNVs.tsv.gz exomiser.hg38.cadd-in-del-path=${exomiser.data-directory}/cadd/${cadd.version}/gnomad.genomes.r4.0.indel.tsv.gz ``` -------------------------------- ### Example Genes TSV Output Source: https://exomiser.readthedocs.io/en/stable/_sources/result_interpretation.rst.txt Sample content from a genes.tsv file showing how genes like MUC6 can appear multiple times under different MOI models. ```text #RANK ID GENE_SYMBOL ENTREZ_GENE_ID MOI P-VALUE EXOMISER_GENE_COMBINED_SCORE EXOMISER_GENE_PHENO_SCORE EXOMISER_GENE_VARIANT_SCORE HUMAN_PHENO_SCORE MOUSE_PHENO_SCORE FISH_PHENO_SCORE WALKER_SCORE PHIVE_ALL_SPECIES_SCORE OMIM_SCORE MATCHES_CANDIDATE_GENE HUMAN_PHENO_EVIDENCE MOUSE_PHENO_EVIDENCE FISH_PHENO_EVIDENCE HUMAN_PPI_EVIDENCE MOUSE_PPI_EVIDENCE FISH_PPI_EVIDENCE 1 FGFR2_AD FGFR2 2263 AD 0.0000 0.9981 1.0000 1.0000 0.8808 1.0000 0.0000 0.5095 1.0000 1.0000 0 Jackson-Weiss syndrome (OMIM:123150): Brachydactyly (HP:0001156)-Broad hallux (HP:0010055), Craniosynostosis (HP:0001363)-Craniosynostosis (HP:0001363), Broad thumb (HP:0011304)-Broad metatarsal (HP:0001783), Broad hallux (HP:0010055)-Broad hallux (HP:0010055), Brachydactyly (HP:0001156)-abnormal sternum morphology (MP:0000157), Craniosynostosis (HP:0001363)-premature cranial suture closure (MP:0000081), Broad thumb (HP:0011304)-abnormal sternum morphology (MP:0000157), Broad hallux (HP:0010055)-abnormal sternum morphology (MP:0000157), Proximity to FGF14 associated with Spinocerebellar ataxia 27 (OMIM:609307): Broad hallux (HP:0010055)-Pes cavus (HP:0001761), Proximity to FGF14 Brachydactyly (HP:0001156)-abnormal digit morphology (MP:0002110), Broad thumb (HP:0011304)-abnormal digit morphology (MP:0002110), Broad hallux (HP:0010055)-abnormal digit morphology (MP:0002110), 2 ENPP1_AD ENPP1 5167 AD 0.0049 0.8690 0.5773 0.9996 0.6972 0.5773 0.5237 0.5066 0.6972 1.0000 0 Autosomal recessive hypophosphatemic rickets (ORPHA:289176): Brachydactyly (HP:0001156)-Genu varum (HP:0002970), Craniosynostosis (HP:0001363)-Craniosynostosis (HP:0001363), Broad thumb (HP:0011304)-Tibial bowing (HP:0002982), Broad hallux (HP:0010055)-Genu varum (HP:0002970), Brachydactyly (HP:0001156)-fused carpal bones (MP:0008915), Craniosynostosis (HP:0001363)-abnormal nucleus pulposus morphology (MP:0006392), Broad thumb (HP:0011304)-fused carpal bones (MP:0008915), Broad hallux (HP:0010055)-fused carpal bones (MP:0008915), Craniosynostosis (HP:0001363)-ceratohyal cartilage premature perichondral ossification, abnormal (ZP:0012007), Broad thumb (HP:0011304)-cleithrum nodular, abnormal (ZP:0006782), Proximity to PAPSS2 associated with Brachyolmia 4 with mild epiphyseal and metaphyseal changes (OMIM:612847): Brachydactyly (HP:0001156)-Brachydactyly (HP:0001156), Broad thumb (HP:0011304)-Brachydactyly (HP:0001156), Broad hallux (HP:0010055)-Brachydactyly (HP:0001156), Proximity to PAPSS2 Brachydactyly (HP:0001156)-abnormal long bone epiphyseal plate morphology (MP:0003055), Craniosynostosis (HP:0001363)-domed cranium (MP:0000440), Broad thumb (HP:0011304)-abnormal long bone epiphyseal plate morphology (MP:0003055), Broad hallux (HP:0010055)-abnormal long bone epiphyseal plate morphology (MP:0003055), // 7 MUC6_AD MUC6 4588 AD 0.0096 0.7532 0.5030 0.9990 0.0000 0.0000 0.0000 0.5030 0.5030 1.0000 0 Proximity to GKN2 Brachydactyly (HP:0001156)-brachydactyly (MP:0002544), Broad thumb (HP:0011304)-brachydactyly (MP:0002544), Broad hallux (HP:0010055)-brachydactyly (MP:0002544), 8 MUC6_AR MUC6 4588 AR 0.0096 0.7531 0.5030 0.9990 0.0000 0.0000 0.0000 0.5030 0.5030 1.0000 0 Proximity to GKN2 Brachydactyly (HP:0001156)-brachydactyly (MP:0002544), Broad thumb (HP:0011304)-brachydactyly (MP:0002544), Broad hallux (HP:0010055)-brachydactyly (MP:0002544), ``` -------------------------------- ### Configure Data Directory Source: https://exomiser.readthedocs.io/en/stable/_sources/installation.rst.txt Settings for specifying the custom data directory path and verifying its structure. ```properties exomiser.data-directory=/data/exomiser-data ``` ```bash /data/exomiser-data/ ├── 2512_hg19 ├── 2512_hg38 └── 2512_phenotype ``` ```properties exomiser.data-directory=/data/exomiser-data exomiser.hg19.data-version=2512 exomiser.phenotype.data-version=2512 ``` ```properties exomiser.data-directory=/data/exomiser-data exomiser.hg38.data-version=2512 exomiser.phenotype.data-version=2512 ``` ```properties exomiser.data-directory=/data/exomiser-data exomiser.hg19.data-version=2512 exomiser.hg38.data-version=2512 exomiser.phenotype.data-version=2512 ``` -------------------------------- ### Run Exomiser with genome preset Source: https://exomiser.readthedocs.io/en/stable/input_files_and_options.html Use the genome preset for WGS samples; requires REMM score data configuration. ```bash java -jar exomiser-cli-15.1.0.jar analyse --sample path/to/phenopacket.json --preset genome ``` -------------------------------- ### Run Exomiser Analysis via CLI Source: https://exomiser.readthedocs.io/en/stable/input_files_and_options.html Executes an exome analysis using a specified YAML configuration file. ```bash java -jar exomiser-cli-15.1.0.jar analyse --analysis examples/test-analysis-exome.yml ```