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tierup
tierup reanalyses Tier 3 variants in undiagnosed GeL rare disease cases.
tierup answers the following questions derived from the GeL tiering rules:
  • Is the variant in a green gene in a panel app panel assigned to the case?
  • Does the variant mode of inheritance match the gene's in the panel app panel?
Tier 3 variants that meet these criteria are labelled 'tier_1' or 'tier_2' in the tier_tierup field of the tierup output CSV.

Installation

pip install jellypy-tierup

Guides

Reanalyse Tier 3 variants in a GeL rare disease case

  1. 1.
    Create a configuration file with CIPAPI details. For example:
    # config.ini
    [pyCIPAPI]
    client_id = YOUR-GEL-CLIENT-ID
    client_secret = YOUR-GEL-CLIENT-SECRET
  2. 2.
    Run tierup For example, interpretation request 1234 version 2 could be analysed with:
    tierup --irid 1234 --irversion 1 --config config.ini
    If the intepretation request data is available locally in json format, then you can pass the file directly:
    tierup -j interpretation_request.json --config config.ini
  3. 3.
    View results
    • *.tierup.csv - The tier_tierup column in the results file contains the new variant tier determined by tierup. Each row is a report event for a variant in the proband. Note: The same variant may have multiple report events depending on the number of assigned gene panels, mode of inheritance and penetrance models analysed.

TierUp output fields (*.tierup.csv)

Field
Description
interpretation_request_id
Identifier for GeL case
tier_tierup
Tiering result from tierup: tier_3_not_in_panel, tier_3_red_or_amber, tier_3_green_moi_mismatch, tier_2, tier_1
tier_gel
Initial GeL tier. Previously tier field in tierup 0.2.0
assembly
Reference genome
chromosome
Chromosome number
position
Genomic coordinate
reference
Reference allele
alternate
Proband Alternate allele
consequences
Sequence ontology terms for the variant consequences in all relevant transcripts
zygosity
Zygosity in the proband
segregation
Pattern calculated using genotypes from family members
penetrance
Penetrance model used to assess the variant
tiering_moi
Mode of inheritance for the variant in the proband. Previously inheritance field in tierup 0.2.0
tu_panel_hash
Panel unique hash id used in TierUp analysis
tu_panel_name
Panel name used in TierUp analysis
tu_panel_version
Panel version used in TierUp analysis
tu_panel_number
Panel id used in TierUp analysis
tu_panel_created
The date the panel version used in TierUp analysis was created
tu_run_time
Time TierUp was initiated

Constraints

  • tierup input is limited to undiagnosed rare disease cases. The tool therefore raises an error if users attempt to process a solved case.
  • Access to case data from GeL is only possible on the HSCN
  • Interpretation request data must comply with the GeL v6 interpretation request model
  • tierup does not analyse CNVs
  • tierup does not account for information on variant penetrance

Support

Please raise issues, message the #jellypy slack channel or send an email.