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.
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-SECRETRun tierup For example, interpretation request 1234 version 2 could be analysed with:
tierup --irid 1234 --irversion 1 --config config.iniIf the intepretation request data is available locally in json format, then you can pass the file directly:
tierup -j interpretation_request.json --config config.iniView results
*.tierup.csv - The
tier_tierupcolumn 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.
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 |
pa_ensembl | Ensembl identifier for the gene in panelapp panel |
pa_hgnc_id | HGNC ID from the panel app panel |
pa_gene | Gene symbol from the panel app panel |
pa_moi | Mode of inheritance for the gene in the panelapp panel version |
pa_confidence | 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. |
extra_panels | Panel ID pointers updated via TierUp check for depreciated Panels in GeL directory |
re_id | Unique identifier for the report event. Previously event_id field in tierup 0.2.0 |
re_panel_id | Report event panel id |
re_panel_version | Report event panel version |
re_panel_source | Report event panel source. All expected to be panelapp |
re_panel_name | Report event panel name |
re_gene | Report event gene symbol |
justification | GeL eventJustification field which describes why the variant was tiered |
created_at | Creation date for the GeL interpreted genome was created |
software_versions | Software versions used in the GeL analysis |
reference_db_versions | Reference database versions used int he GeL analysis |
tu_version | jellypy-tierup version used to generate results |
tierupinput 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
tierupdoes not analyse CNVstierupdoes not account for information on variant penetrance
Please raise issues, message the #jellypy slack channel or send an email.
