Homing in on Clinically Relevant Variants with the BlueBee Annotation Reference Pipeline

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Available to all BlueBee users, the BlueBee Annotation Reference Pipeline enables the identification of a large number of genetic variants from a single sequencing experiment. Understanding the clinical relevance of the identified variants in any genetic dataset critically depends on annotating those variants with the proper information.

To ensure a fast and efficient variant annotation BlueBee’s Annotation Reference Pipeline gathers content from clinically relevant data sources:

  • ClinVar – public archive of reports of the relationships among human variations and phenotypes, with supporting evidence
  • 1000 Genomes – a deep catalog of Human Genetic Variation
  • Ensembl – database with stored areas of the genome that differ between individual genomes
  • gnomAD -The Genome Aggregation Database
  • ACMG SF v2.0 – The recommendations for reporting of secondary findings in clinical exome and genome sequencing
  • SIFT – the algorithm to predict the effects of coding non-synonymous variants on protein function
  • PROVEAN – a software tool which predicts whether an amino acid substitution or indel has an impact on the biological function of a protein
  • MutationsTaster – the web-based application to evaluate DNA sequence variants for their disease-causing potential
  • Mutation Assessor – a server that predicts the functional impact of amino-acid substitutions in proteins
  • FATHMM – a high-throughput web-server that predicts functional consequences of identified variants
  • dbNSFP – database with functional prediction and annotation of all potential non-synonymous SNVs
  • dbSNP - a single database that contains all identified genetic variations

The Annotation Pipeline – released in September this year – supports researchers and clinicians in their efforts to home in on a clinically relevant set of variants, and to understand their associations with a disease at the protein and molecular network level. The pipeline annotates each variant with a predicted pathogenicity score to simplify and streamline the selection process:

Tools and parameters of the pipeline can be adjusted within the BlueBee platform and users can redefine the pipeline to ‘kick start’ customization.

Input and output files

Below you can see the input and different type of output files that can support different users of your department:

  • Input file: .vcf files
  • Output files: .tsv, .vcf, and .txt
  • Genomic build supported: GRCh37

Each pipeline is reviewed by BlueBee bioinformatics team every 6 months.