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.
pip install jellypy-tierup
Create a configuration file with CIPAPI details. For example:
# config.ini[pyCIPAPI]client_id = YOUR-GEL-CLIENT-IDclient_secret = YOUR-GEL-CLIENT-SECRET
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
*.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.
Identifier for GeL case
Tiering result from tierup: tier_3_not_in_panel, tier_3_red_or_amber, tier_3_green_moi_mismatch, tier_2, tier_1
Initial GeL tier. Previously tier field in tierup 0.2.0
Proband Alternate allele
Sequence ontology terms for the variant consequences in all relevant transcripts
Zygosity in the proband
Pattern calculated using genotypes from family members
Penetrance model used to assess the variant
Mode of inheritance for the variant in the proband. Previously inheritance field in tierup 0.2.0
Panel unique hash id used in TierUp analysis
Panel name used in TierUp analysis
Panel version used in TierUp analysis
Panel id used in TierUp analysis
The date the panel version used in TierUp analysis was created
Time TierUp was initiated
Ensembl identifier for the gene in panelapp panel
HGNC ID from the panel app panel
Gene symbol from the panel app panel
Mode of inheritance for the gene in the panelapp panel version
Current gene confidence level from the latest version of the panel app panel: 4 or 3 = Green; 2 = Amber; 1 or 0 = Red; Green genes indicate TieredUp variant.
Panel ID pointers updated via TierUp check for depreciated Panels in GeL directory
Unique identifier for the report event. Previously event_id field in tierup 0.2.0
Report event panel id
Report event panel version
Report event panel source. All expected to be panelapp
Report event panel name
Report event gene symbol
GeL eventJustification field which describes why the variant was tiered
Creation date for the GeL interpreted genome was created
Software versions used in the GeL analysis
Reference database versions used int he GeL analysis
jellypy-tierup version used to generate results
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