Data and Software Resources

Children’s Mercy Variant Warehouse Database

A variant warehouse of non-identifiable, summary data on all variants identified in the Children’s Mercy Genomic Medicine Center is publicly available in the Children's Mercy Variant Warehouse Database. The database can be searched and viewed with genomic annotations, population database cross-references such as ClinVar, gnomAD and dbSNP, ACMG curations and a local allele frequency.  Variant data are available for bulk download as an annotated VCF. The database is updated quarterly.

VIKING software

VIKING (Variant Integration and Knowledge Interpretation in Genomes) is software for variant interpretation and reporting. VIKING allows medical geneticists to view variants for an individual patient or family along with the characterization information produced by the RUNES software.  It enables users to review millions of variants detected in each individual by providing dynamic filters to search by variant category, gene, minor allele frequency and variant quality. 

VIKING provides tools to analyze results from a patient and family members to identify potentially diagnostic variants using inheritance patterns. Once identified, variants of interest can be categorized and added to customized reports.

RUNES software

The Children's Mercy variant characterization pipeline (RUNES: Rapid Understanding of Nucleotide variant Effect Software) is a multi-stage analysis pipeline for annotating and classifying human nucleotide variation.

Characterization process

Characterization is divided into multiple independent stages that record zero or more annotations for each variant according to the type of characterization being performed by the stage. Variant effect is predicted using in silico prediction tools and cross-referencing with external databases. The stages include:

• ENSEMBL Variant Effect Predictor (VEP)
• CMH splice impact evaluator
• CMH transcript context characterizer
• Mitochondrial gene context characterizer
• Comparison with external databases:
  • dbSNP
  • Human Gene Mutation Database (HGMD)
  • ClinVar
  • Genome Aggregation Database (gnomAD)
  • Exome Aggregation Consortium (ExAC)
  • Catalog of Somatic Mutations in Cancer (COSMIC)

Variant classification

At the end of characterization, variant annotations are aggregated and submitted to a variant classifier. The classifier assigns a severity category to each variant based on the accumulated evidence, with the most damaging category kept as the final categorization. The categories and criteria include:

Category 1

Category 2

Category 3

Category 4

Category 5

Astrolabe software

Astrolabe is software for translating whole genome sequence data into pharmacogenetic information that can be used to guide medication selection, dosing and prescription. Clinicians and researchers can use this information to reduce adverse drug events and maximize medication efficacy.

Pharmacogenetic allele identification

Ongoing pharmacogenetic research defines drug/gene connections and maps drug response to specific alleles. Gene alleles are defined by specific genetic variants and assigned identifiers that form an allele nomenclature that is used by public and private resources to connect variation to gene activity.

Astrolabe takes genetic variants and sequences generated by whole genome, whole exome and targeted panel sequencing and compares it to the catalog of pharmacogenetic alleles to determine which pair of alleles a patient carries.

Astrolabe was initially developed for the CYP2D6 gene, then extended to CYP2C9 and CYP2C19 with additional genes in the process of being validated. Astrolabe is integrated with the PharmVar (Pharmacogene Variation Consortium) database, a National Institutes of Health-funded project produced as a collaboration between the Children’s Mercy Clinical Pharmacology program and the Center for Pediatric Genomic Medicine.