AION guide

AION - Instructions for Use

AION Release Notes

Updates to the annotation sources are not logged here.

Version 3.15.1.5 - CE-labeled (IVDD)

Release date: 15/March/2025

Highlights of changes:

Minor bug fix

Version 3.15.1.4 - CE-labeled (IVDD)

Release date: 07/March/2025

Highlights of changes:

Minor infrastructure maintenance
Minor bug fix

Version 3.15.1.3 - CE-labeled (IVDD)

Release date: 27/February/2025

Highlights of changes:

Minor bug fixes

Version 3.15.1.2 - CE-labeled (IVDD)

Release date: 21/February/2025

Highlights of changes:

Minor bug fixes

Version 3.15.1.1 - CE-labeled (IVDD)

Release date: 15/January/2025

Highlights of changes:

Minor bug fix.

Version 3.15.1.0 - CE-labeled (IVDD)

Release date: 15/January/2025

Highlights of changes:

Minor bug fixes.
Coverage information update for non-coding genes
Data Sources Update

Version 3.15.0.0 - CE-labeled (IVDD)

Release date: 19/December/2024

Highlights of changes:

Coverage information tab in the UI
Data Sources Update
Case filtering by status
Minor bug fixes.

Version 3.14.1.4 - CE-labeled (IVDD)

Release date: 16/December/2024

Highlights of changes:

Minor bug fixes.

Version 3.14.1.3 - CE-labeled (IVDD)

Release date: 12/December/2024

Highlights of changes:

Minor bug fixes.

Version 3.14.1.2 - CE-labeled (IVDD)

Release date: 10/December/2024

Highlights of changes:

Minor bug fixes.

Version 3.14.1.1 - CE-labeled (IVDD)

Release date: 03/December/2024

Highlights of changes:

Minor bug fixes.

Version 3.14.1.0 - CE-labeled (IVDD)

Release date: 29/November/2024

Highlights of changes:

Gene coverage information in the UI for cases launched from internal secondary analysis pipeline.
Minor bug fixes.

Version 3.14.0.0 - CE-labeled (IVDD)

Release date: 26/November/2024

Highlights of changes:

Introduction of AION Smoking guns and AION Clues in AION results for small variants.
gnomAD v4.1.0 used for variant priorization.
Introduction of viewer only users.
Inclusion of gene coverage information.
Minor bug fixes.

Version 3.13.1.3 - CE-labeled (IVDD)

Release date: 1/October/2024

Highlights of changes:

Minor bug fix.

Version 3.13.1.2 - CE-labeled (IVDD)

Release date: 30/September/2024

Highlights of changes:

Minor bug fixes.

Version 3.13.1.1 - CE-labeled (IVDD)

Release date: 17/September/2024

Highlights of changes:

Maintenance infrastructure improvement
Minor bug fix.

Version 3.13.1.0 - CE-labeled (IVDD)

Release date: 5/September/2024

Highlights of changes:

Minor bug fixes.
Improvement on case search functionality.

Version 3.13.0.1 - CE-labeled (IVDD)

Release date: 12/August/2024

Highlights of changes:

Minor bug fix.

Version 3.13.0.0 - CE-labeled (IVDD)

Release date: 7/August/2024

Highlights of changes:

Case search functionality
CNV relevant variants optimization
Minor bugs fixes

Version 3.12.3.1 - CE-labeled (IVDD)

Release date: 25/July/2024

Highlights of changes:

Minor bug fix.

Version 3.12.3.0 - CE-labeled (IVDD)

Release date: 25/July/2024

Highlights of changes:

Data sources update: inclusion of gnomAD v4.1.0
Minor bugs fixes.

Version 3.12.2.2 - CE-labeled (IVDD)

Release date: 16/July/2024

Highlights of changes:

Minor bugs fixes.

Version 3.12.2.1 - CE-labeled (IVDD)

Release date: 11/July/2024

Highlights of changes:

Minor bugs fixes.

Version 3.12.2.0 - CE-labeled (IVDD)

Release date: 10/July/2024

Highlights of changes:

Minor infrastructure maintenance

Version 3.12.1.1 - CE-labeled (IVDD)

Release date: 25/June/2024

Highlights of changes:

Minor bug fix

Version 3.12.1.0 - CE-labeled (IVDD)

Release date: 24/June/2024

Highlights of changes:

Activation/Inactivation of cases functionality
Minor bugs fix

Version 3.12.0.2 - CE-labeled (IVDD)

Release date: 11/June/2024

Highlights of changes:

Minor infrastructure maintenance.

Version 3.12.0.1 - CE-labeled (IVDD)

Release date: 03/June/2024

Highlights of changes:

Minor bugs fixes.

Version 3.12.0.0 - CE-labeled (IVDD)

Release date: 30/May/2024

Highlights of changes:

Annotation data update
Minor bugs fixes.

Version 3.11.1.1 - CE-labeled (IVDD)

Release date: 16/May/2024

Highlights of changes:

Upgrade to support increased AION usage.

Version 3.11.1.0 - CE-labeled (IVDD)

Release date: 16/May/2024

Highlights of changes:

Minor bugs fix in filtering and variant classification.
Ability to Refresh stats in the AION DB.

Version 3.11.0.2 - CE-labeled (IVDD)

Release date: 8/May/2024

Highlights of changes:

Minor bug fix in gene to disease association.

Version 3.11.0.1 - CE-labeled (IVDD)

Release date: 2/May/2024

Highlights of changes:

Minor bug fix relating authentication issues in integrated services

Version 3.11.0.0 - CE-labeled (IVDD)

Release date: 25/April/2024

Highlights of changes:

Data update for ClinVar and CNV annotations
Link to IGV viewer application added
Minor bugs fixes

Version 3.10.0.3 - CE-labeled (IVDD)

Release date: 10/April/2024

Highlights of changes:

Improvement on information display in the user interface
Bug fix on Advanced Filtering results filtering and display

Version 3.10.0.2 - CE-labeled (IVDD)

Release date: 08/April/2024

Highlights of changes:

Bug fix in showing status of the affectedness of parents

Version 3.10.0.1 - CE-labeled (IVDD)

Release date: 04/April/2024

Highlights of changes:

Bug fixes and new CNV file format support

Version 3.10.0.0 - CE-labeled (IVDD)

Release date: 26/March/2024

Highlights of changes:

Ability to manually classifiy small variants and store comments for each variant classification
Ability to store small variants manual variant classification and VCF variants in an internal AION DB from every case, and use this variant information in new cases.

Version 3.9.6.0 - CE-labeled (IVDD)

Release date: 3/March/2024

Highlights of changes:

Silent release on functionality to support segregation/trio analyiss for CNVs pipeline

Version 3.9.5.1 - CE-labeled (IVDD)

Release date: 21/February/2024

Highlights of changes:

Fix on Manual Classification tabs display

Version 3.9.5.0 - CE-labeled (IVDD)

Release date: 21/February/2024

Highlights of changes:

Support to combined vcf files (SNV and CNV)
Small fixes and improvements for
1. Layout for small variant cards
2. Case status
3. Advanced filters

Version 3.9.4.2 - CE-labeled (IVDD)

Release date: 13/February/2024

Highlights of changes:

1. Fix in report downloading

Version 3.9.4.1 - CE-labeled (IVDD)

Release date: 9/February/2024

Highlights of changes:

1. Fix in report downloading

Version 3.9.4.0 - CE-labeled (IVDD)

Release date: 8/February/2024

Highlights of changes:

Filtering by disease inheritance and patient-disease phenotype match available on both SNV & CNV table views through advanced filters.
UX improvement for filtering
IVDB based filtering by introducing column level filters on the numeric data from IVDB
Small fix on long gene list input in advanced filters

Version 3.9.3.1 - CE-labeled (IVDD)

Release date: 24/January/2024

Highlights of changes:

Fix of issues related filtering by Empty through advanced filters
Dictionary fix to always keep the highest confidence for g2d association from a source
Small fixes to advanced filtering and long username overflow issue

Version 3.9.3.0 - CE-labeled (IVDD)

Release date: 15/January/2024

Highlights of changes:

Introducing filtering based on IVDB data in the advanced filtering
Visualisation of source and confidence information related the gene-disease-MOI associations in the UI
Usability enhancements and fixes to advanced filtering functionality

Version 3.9.2.1 - CE-labeled (IVDD)

Release date: 5/January/2024

Highlights of changes:

Fixing issue related concurrent CNV runs

Version 3.9.2.0 - CE-labeled (IVDD)

Release date: 20/December/2023

Highlights of changes:

Introducing advanced filtering in AION. Build filter queries, save them into a reusable filter and apply quickly to all your cases across the platform. Advanced filters are available on both SNV and CNV manual filtering view and users can create their own private filters or share them with the whole organisation.
Quality hard filters are now removed from the SNV annotation process, so all variants of the analysed regions where FILTER=PASS or “.” , regardless of quality ( DP, VAF ) will get annotated and are available on SNV manual filtering view for analysis.
The filterable values are now static on SNV and CNV manual filtering column filters.

Version 3.9.1.0 - CE-labeled (IVDD)

Release date: 13/December/2023

Highlights of changes:

Minor improvements and bug fixes in the pipeline

Version 3.9.0.0 - CE-labeled (IVDD)

Release date: 29/November/2023

Highlights of changes:

New version of the dictionaries used for gene to disease to mode of inheritance associations.
Minor bug fixes in the UI
Support for CNV vcf files with only one field in the FORMAT column

Version 3.8.5.1 - CE-labeled (IVDD)

Release date: 21/November/2023

Highlights of changes:

Fix of bug affecting segregation information in subset of trio cases with an affected parent

Version 3.8.5.0 - CE-labeled (IVDD)

Release date: 16/November/2023

Highlights of changes:

New design in the final report
Support for CNVpytor VCF file format as well as DragenCNV with 0 POS

Version 3.8.4.1 - CE-labeled (IVDD)

Release date: 6/November/2023

Highlights of changes:

CNV pipeline gnomAD SV threshold for relevant tab filtering corrected to 0.01
Hubspot chatbot added
Updated transcript file for hg19 to ensure always showing the latest version
Small UI improvements

Version 3.8.4.0 - CE-labeled (IVDD)

Release date: 31/October/2023

Highlights of changes:

New canonical transcript files
Bug fix to gnomAD SV hg38 data liftover
Small UI fixes

Version 3.8.3.1 - CE-labeled (IVDD)

Release date: 23/October/2023

Highlights of changes:

Bug fix to long indel visualisation on AION ranking view
Infrastructure change on storing shared between components ACMG calculator code

Version 3.8.3.0 - CE-labeled (IVDD)

Release date: 17/October/2023

Highlights of changes:

More information added to the UI from gnomAD
Added possibility to generate report in Spanish language
Bug fix to correct uncontinuos ranking

Version 3.8.2.0 - CE-labeled (IVDD)

Release date: 9/October/2023

Highlights of changes:

Updated Global frequent artifact blacklist for hg38 cases
Update to the PVS1 gene file and annotation strategy
Update to handling of high frequent whitelisted variants
IVDB refresh endpoint memory issue fix

Version 3.8.1.1 - CE-labeled (IVDD)

Release date: 3/October/2023

Highlights of changes:

Fix to the case history version numbering schema

Version 3.8.1.0 - CE-labeled (IVDD)

Release date: 2/October/2023

Highlights of changes:

Introducing ability to edit patient phenotype directly from the case page and recalculate results
Internal variant database data loading related bug fixes and improvements

Version 3.8.0.1 - CE-labeled (IVDD)

Release date: 20/September/2023

Highlights of changes:

Fixed style of AION ranking tooltip
Removed unavailable file to download for CNV-only cases
Re-added manual link missing to case submit page

Version 3.8.0.0 - CE-labeled (IVDD)

Release date: 19/September/2023

Highlights of changes:

Native annotation support in GRCh38 for small variants, including gnomAD 3.1 and MANE Select transcript
CNVs can now be analysed in GRCh38 as well
Support for more CNV input formats
Changes on submit case flow and submit case form allowing the possibility to submit CNVs only

Version 3.7.1.0 - CE-labeled (IVDD)

Release date: 4/September/2023

Highlights of changes:

High quality variants in CNV table is now called relevant variants and combines filtering criteria for quality + gnomAD SV allele frequency of known cnvs overlapping
UI fixes to CNV view

Version 3.7.0.1 - CE-labeled (IVDD)

Release date: 21/August/2023

Highlights of changes:

Small UI fixes to CNV manual filtering view
Bug fix for symptoms comparison dialog on CNV drawer

Version 3.7.0.0 - CE-labeled (IVDD)

Release date: 14/August/2023

Highlights of changes:

UI and manual filtering functionality for CNV results
1. CNV results are now visualised and available for manual filtering in a new CNV manual filtering view.

Version 3.6.0.4 - CE-labeled (IVDD)

Release date: 20/July/2023

Highlights of changes:

Bug fix to correct jointcalling for multiallelic variants and liftover

Version 3.6.0.3 - CE-labeled (IVDD)

Release date: 19/July/2023

Highlights of changes:

Bug fix to normalisation step

Version 3.6.0.2 - CE-labeled (IVDD)

Release date: 6/July/2023

Highlights of changes:

Update of gene panels available by default

Version 3.6.0.1 - CE-labeled (IVDD)

Release date: 30/June/2023

Highlights of changes:

AWS batch scaling optimisation

Version 3.6.0.0 - CE-labeled (IVDD)

Release date: 22/June/2023

Highlights of changes:

New version of gene-disease-phenotype dictionaries
New version of artifact denylist
Small improvements to pipeline and infrastructure

Version 3.5.0.4 - CE-labeled (IVDD)

Release date: 9/June/2023

Highlights of changes:

FE bug fixes

Version 3.5.0.3 - CE-labeled (IVDD)

Release date: 8/June/2023

Highlights of changes:

FE bug fixes

Version 3.5.0.2 - CE-labeled (IVDD)

Release date: 7/June/2023

Highlights of changes:

Improved error messaging from pipeline
Bug fixes.

Version 3.5.0.1 - CE-labeled (IVDD)

Release date: 31/May/2023

Highlights of changes:

CNV output formatting, pipeline bug fixes
FE bug fixes.

Version 3.5.0.0 - CE-labeled (IVDD)

Release date: 25/May/2023

Highlights of changes:

Users can now run AION without HPO terms assigned to the case. We strongly suggest to include them to keep high ranking specificity

Version 3.4.0.0 - CE-labeled (IVDD)

Release date: 23/May/2023

Highlights of changes:

AION now annotates CNV/SV variants provided with VCF files and prioritises them with ACMG criteria. See more details in the VCF format
UI improvements on case page:
1. Supporting input file review and download
2. Introducing fixed case header for better contextual information
Archive functionality is now called delete to avoid confusions
Enabling internal variant database statistics in manual filtering view

Version 3.3.1.0 - CE-labeled (IVDD)

Release date: 17/May/2023

Highlights of changes:

Implemented snackbar and maintenance screen to inform users of releases and maintenance periods

Version 3.3.0.0 - CE-labeled (IVDD)

Release date: 27/April/2023

Highlights of changes:

Improved annotation infrastructure
Improved gnomAD frequency annotation considering genome reference versions.
Improved NMD, functional domain, Clinvar hotspot as well as splicing annotation
Update of Clinvar gene lists (PVS1, PP2, BP1)
Improvement of ACMG criteria (PS1, PM5, PM1, BP3)

Version 3.2.4.0 - CE-labeled (IVDD)

Release date: 12/April/2023

Highlights of changes:

Customer-specific internal variant database for small variants (SNPs and Indels)

Version 3.2.3.0 - CE-labeled (IVDD)

Release date: 16/March/2023

Highlights of changes:

Reference genome of input files is asked when submitting a case. The user input is verified with the data in VCF and the user is informed about conflicts
Manual filtering view now informs of number of variants passing the search & filter criteria
Small FE improvements

Version 3.2.2.0 - CE-labeled (IVDD)

Release date: 9/March/2023

Highlights of changes:

Update of VEP version and annotation infrastructure
Infinite scrolling on manual filtering view to improve UX
Ability to archive cases
Small FE improvements
Detailed list
1. Update of annotation pipeline includes running VEP on the fly. The VEP version used is 108.

Version 3.2.1.1 - CE-labeled (IVDD)

Release date: 20/Feb/2023

Highlights of changes:

Adding ZenDesk for customer support
Small FE improvements

Version 3.2.1.0 - CE-labeled (IVDD)

Release date: 6/Feb/2023

Highlights of changes:

Update to ClinVar (21/01/2023) and disease dictionaries (01/2023)
Improvements to ACMG and ClinVar classification implementation
Small FE fixes

Detailed list
Improvements:
1. Updated ClinVar to newest release and updated internal ClinVar truth
2. Updated ACMG Benign rules (BA1, BS1, BS2)
3. Updated ACMG Pathogenic rules (PM4)
4. Update whitelist of high frequently variants from full genes to variants
5. Update variant filters
6. Update of databases relating gene, disease and phenotype dictionaries
7. Improvement of cosegregation consideration

Version 3.2.0.4 - CE-labeled (IVDD)

Release date: 1/Feb/2023

Highlights of changes:

Bug fixed concerning reporting for old cases
Terminology changes on login screen

Version 3.2.0.3 - CE-labeled (IVDD)

Release date: 24/Jan/2023

Highlights of changes:

Bug fixed concerning running cases with only few variants with partial annotations.

Version 3.2.0.2 - CE-labeled (IVDD)

Release date: 23/Jan/2023

Highlights of changes:

Filtering on a column in the manual variant filtering view will only show options from the available current column values
When sorting and filtering, sorting tags show “Sort by:” and appear first
Removed the ability to add HPO terms to parents to avoid confusion.
Fixed a bug preventing correct sorting by position
Removed Intercom plugin

Detailed list

Bugs
1. Fixed error preventing tag in gene filter header from changing to “Applied” only when the filters were applied
2. Fixed error when filtering of ClinVar column by 'Conflicting interpretation'
3. Fixed message if no variants were found in the AION ranking
4. Fixed issue showing negative GQ values caused by integer overflow
5. Fixed issue causing non-unique HPO terms for cases created through API (didn’t affect users)
6. Fix workflow and script for rd-aion-wrapper deployment through github actions
7. Fixed minor bug in reading 'summary'
8. Fixed minor bug in reading 'case_info'
Improvements

1. Installed Hotjar
2. Improved annotation pipeline with refactorings
3. Improved system usage
4. Added relaunch case API to facilitate benchmarking and testing

Version 3.2.0.1 - CE-labeled (IVDD)

Release date: 18/Jan/2023

Highlights of changes:

Bug fixed concerning variants not being added to the report from the manual variant filtering view.

Version 3.2.0.0 - CE-labeled (IVDD)

Release date: 16/Jan/2023

Highlights of changes:

Added manual filtering view for browsing and reporting annotated variants
In silico panels feature allowing restricting the analysed regions when submitting the AION analysis. Similar in silico panel and gene filters are available also on the manual filtering view for subsetting the annotated variants
Improved consideration of affectedness of parents in trios and implementation of ACMG criteria related to cosegregation (PP1, BS4)
AION pathogenicity classification calibrated into the following classes: Benign, Likely Benign, VUS, Likely pathogenic, Pathogenic
Improved deny list of frequently seen artefacts to reduce number of prioritised artefacts
Added patch version to AION version

Detailed list

Bugs
1. Investigation: fix CH logic for AR diseases with clear CH pathogenic variants
2. Manual processing should error/warn of obsolete HPOs
3. If vcf file is empty after downsampling, print proper error/warning
4. Support analysing vcf with 1 only variant after downsampling
5. Fix cosegregation_rank for CH without partner
6. HPO in inheritance column for customer sample
Improvements

1. Implement segregation part for ACMG - PP1
2. Implement segregation part for ACMG - BS4
3. New filter: variants with MOI = AD and segregation = maternal or paternal
4. Add CH fishing logic for Tier Null variants
5. Skip PS2 for non joint called trios
6. Include patient HPO terms in prioritizer file
7. Curation of disease entries in our catalogue containing "susceptibility", "resistance", or being associated to expansions \+ strategy to include/exclude related diseases
8. Change message if no variants were found in the AION ranking
9. Add BS2 BA1 as mutually exclusive

Version 3.1.0 - CE-labeled (IVDD)

Release date: 7/Nov/2022

Highlights of changes:

Updated UI for case table, submit process, case details and variant cards
Updated ACMG implementation:
1. Implementation of PS2, PVS1, PM2, PM3, PM6
2. The user can now apply/remove criteria as they see fit and the ACMG prediction is dynamically updated
3. Criteria applied automatically by the AI can also be overruled and are marked with a symbol for explicability
4. ACMG criteria grouped by segregation, disorder, effect, computational and functional, gene and region, frequency, other databases
Disease symptoms are now shown and those shared between the disease and the case are highlighted for improved explicability
Show compound heterozygous variants next to each other
Updated data dictionaries relating variants, genes, diseases and phenotype, and MOI
Support hg38 reference genome version through liftover
Support WGS data input through downsampling to exomes ±50bp and known intronic variants
Quality filtering supported as command-line option for the pipeline. Default quality filters used through UI: min-VAF 20, min-DP 10, min-QUAL 0
Add links to Orphanet (for ORPHA diseases), mastermind, OMIM, pubmed search, google scholar search, HPO terms
Improved error reporting on UI side for failed cases
Better UX through progress indicators during upload, process, case details
Improved stability for processing files >1GB
Better explicability of phenotypic similarity through HPOs
Detailed list

Bugs
1. Wrong GTs for deletions after VT decomposition
2. Prioritised file contains variants with filter tags
3. AD read incorrect for multiallelic variants
4. Create downsampling BED files with chr field
5. Identify Tier CH for splice variants
6. Fix sex chromosome segregation edge case
7. Adapt vt normalize and remove any other chromosome not part of autosomal and sexual
Improvements
1. Support for VCF files not having AD but RO, AO fields
2. Improve Compound heterozygous reporting
3. Simplify variant status summary from Clinvar
4. Add new link columns for google scholar and pubmed
5. Get pipeline progress to reflect actual status
6. Modify identification strategy for missing compound heterozygous partners
7. Investigate de novo calling improvements
8. Modularize ACMG calculation
9. Define and implement new annotation file
10. Missing RefSeq Transcript IDs (RefSeq_TranscriptID)
11. Review and fix genes with wrong MOI from sources
12. Include more genes in the white list
13. Fix unsupported MOIs in current dictionaries
14. Relax benign_combo filter
15. Add manually curated gene to disease associations to dictionary
16. Manual curation of MOI for mendelian genes missing MOI info
17. Relax non_pathogenic filter criteria
18. Define more relaxed filters for compound heterozygous variants
19. Remove INFO field from VCF files (before vcf integrity)
20. Include filter-reasoning column in additional unfiltered prioritizer output file
21. Automatically filter unsupported regions to reduce the size of VCF
22. Automatically liftover grch38 files to grch37
23. Define and set a default value for MIN_VAF
24. Update gene panel for mendelian diseases
25. Code refactoring of ACMG to on the fly in aion, integrate with latest AION dev
26. Improve tiering
27. gnomAD hard filters - extended solution
28. Unify column name for ML score (nostos_interpretation, circe)
29. ACMG: uniformize values in output files
30. Include origin from ClinVar (for ACMG - PM6)
31. Review and extend PVS1 & PM6
32. Review use of gnomAD_hom and gnomAD_AC to deprioritize variants
33. Implement ACMG - PM2
34. Implement ACMG - PM6
35. Update Omim to disease dictionary
36. Show intermediate HPO terms that match the patient
37. Implement segregation part for ACMG - PM3
38. Implement segregation part for ACMG - PS
39. Support more VCF formats
40. Add version info to output files
41. Improved normalization of VCF files
42. Implement error/return codes into pipeline logging outputs
43. Add more data to quality report
44. Error coding schema for quality report
45. Remove sorting from join calling
46. Refactoring filtering logic
47. Documentation of the blacklist file
48. Standardize dev environment using docker-compose
49. Integrate script for plots in benchmarking process
50. Generate VCF quality report
51. VAF filter (High-ranking variants in recurring genes (SON, KMT2C...): set quality filter at 20% VAF)
52. Show intermediate HPO terms (ancestors)

Version 3.0.1 - CE-labeled (IVDD)

Release date: 1/Jun/2022

Highlights of changes:

Improvements on the genome build check

Version 3.0.0 - CE-labeled (IVDD)

Release date: 25/May/2022

Highlights of changes:

CE-IVDR certified version
Modularization and dockerization of AION pipeline
Tiering of pedigree cases
Improved scoring and management of compound heterozygous variants
Links to external resources added: RefSeq, Ensemble, Transcripts
Quality module introduced ensuring normalisation as well as handled errors for VCF format
Bugs fixes to increase