# Release notes: Older releases

Major versions Minor versions
v1.9 v1.9.1, v1.9.2
v1.8 v1.8.1, v1.8.2
v1.6 v1.6.1, v1.6.2
v1.4 v1.4.1
v1.3 v1.3.1
v1.1 v1.1.1, v1.1.2

# Version 1.9.2

Release date: 27.04.2020

# Highlights

This release contains a few bug fixes and improvements. Notably, support for the new PubMed page was improved, changing the recommended import procedure to use the new Save option to download the necessary text file (see the documentation for further details):

Figure: New recommended procedure for downloading PubMed references.

# All changes

# Version 1.9.1

Release date: 26.03.2020

# Highlights

This version adds bugfixes and improvements to the finalize variant functionality introduced in version 1.9, support for a new version of VEP, as well as several minor UI improvements.

# All changes

# Finalize variant fixes and improvements

  • Disallow finalize for an analysis when there are unsaved changes in REPORT (CLASSIFICATION page, user must push SUBMIT REPORT first).
  • Added button for undoing changes to REPORT comment on CLASSIFICATION page.
  • Fixed issue where variants present in multiple proband samples within an analysis could not be finalized.

# Support for new VEP version

Added support for updated version of VEP (v98.3), including fixes for:

  • Fetching latest HGNC gene symbol.
  • Choosing the correct RefSeq transcript version. If possible, the version specified in the gene panel is chosen, otherwise the latest available version is used.

# Other UI improvements and bugfixes

  • Added auto-scroll to top in main window when switching between variants in ANALYSES view.
  • Changed HI FREQ and HI COUNT in QUICK mode to display 0 instead of - when all sources report 0 frequency.
  • Adjusted position of modals to allow viewing variant information in top bar when modal is open.
  • Removed COPY ALL TO ALAMUT button.
  • Changed default view in WORK LOG to MESSAGES ONLY.
  • Increased custom gene panel name character limit to 20.
  • Increased height of batch filter box when creating custom gene panels.
  • Adjusted delay for popovers.
  • Improved help text for RIS format import.
  • Fixed word wrap in popover comment fields (ACMG comment and WORK LOG).
  • Fixed an issue causing wrong page height and extra scrollbars.
  • Fixed bug where variants with no transcripts were not filtered on frequency.
  • Fixed an issue where "Worse consequence" warning would show if no consequence was available.

# Version 1.9

Release date: 31.01.2020

# Highlights

This version adds changes to better support larger number of users and user groups using the same variant interpretation database.

# Finalize variants in analyses

The most important change in this version is the addition of a "finalize variant" function in analyses. This allows variant interpretations to be released for overlapping analyses (where the same variant is present in more than one non-finalized analysis workflow) as quickly as possible. This also means that workflow collision warnings are given per variant instead of per analysis, reducing the number of displayed warnings.

With this change, each variant with a new/updated classification in an analysis needs to be finalized by pressing the new FINALIZE button in the CLASSIFICATION section before the analysis (sample) itself can be finalized:

Figure: New button to finalize variant in analysis.

Note that this also needs to be performed for any classification done in QUICK mode, and that interpretations done in VARIANTS mode (stand-alone variants e.g. from search) still need to be finalized as before via the FINISH button in the top bar before the variant is considered truly finalized.

# User group warnings

Finalizing variants means each variant interpretation will be tagged with the main responsible user and user group. This also allows showing a warning if the previous (finalized) variant interpretation was performed by a user from another user group than your own:

Figure: New user group warning.

# Copy text by mouse-click

You can now more easily copy text from many pop-overs by clicking on the text. Look for the clipboard symbol, e.g. in the HGVS cDNA variant name in the top bar:

Figure: New option to copy text directly by mouse-click in popups.

# All changes

  • Finalize variant in analysis
  • Display warning when variant was finalized by different group
  • Mouse popovers and tooltips now use tippy.js (opens new window), with possibility for copying text by mouse-click (any text marked with a clipboard symbol).
  • Optional sections on the ANALYSES OVERVIEW page have been simplified, see ANALYSIS worklist.
  • Added analyses with variants that need verification for optional automatic sorting to NOT READY section on the ANALYSES OVERVIEW page (see Deposit).
  • Added support for importing references with .RIS format from the new PubMed webpage (opens new window).
  • Entries listed in the STUDIES & REFERENCES section are now shown with annotation source and better separation.
  • MARK CLASS 2 button has been removed from the FREQUENCY section (CLASSIFICATION page).
  • Added condition to the Inherited mosaicism filter to exclude cases where the other parent has a normal genotype.
  • ACMG criteria now have short descriptions available everywhere.
  • All action buttons are now disabled until all data has been loaded when opening an analysis.
  • Improve the performance of the region filter
  • Most configuration settings that were previously hard coded in /src/api/config/config.py have now been replaced by a dynamic configuration, set by the environment variable ELLA_CONFIG. See /example_config.yml for examples.
  • Fixed issue during import when re-importing previously deleted analyses.
  • Changes to the documentation, including moving the "Concepts" section to the User manual.

# Version 1.8.2

Release date: 02.12.2019

# All changes

  • Fixed bug where quality filtering did not work for multiple probands.
  • Fixed bug where importing the same sample more than once caused a crash.
  • Fixed bug causing several variants not to be filtered out as they should in the region filter.

# Version 1.8.1

Release date: 30.10.2019

# All changes

  • Fixed bug where users were not able to finalize analyses with reused allele assessments and auto-ignored references under "Pending evaluation".
  • Fixed bug where reference data was not reloaded when including a variant from filtered variants.

# Version 1.8

Release date: 30.10.2019

# Highlights

# Add "other" and unweighted ACMG criteria

Sometimes, criteria that don't match the ACMG guidelines are important for a variant interpretation, e.g. the ENIGMA criteria for the BRCA1/BRCA2 genes. ELLA now allows adding these to the interpretation as a generic OTHER criterion. The type and impact on the classification should be given in this criterion's comment field once added.

In addition, users can often spend significant time evaluating an ACMG criterion for a particular interpretation, but in the end decide that the requirements are not met. ELLA now allows setting an added ACMG criterion as NOT WEIGHTED, so that comments related to this work can be properly recorded.

Figure: The new "other" criterion and unweighted option for ACMG criteria.

Note that neither "other" or unweighted ACMG criteria are counted in the calculation of suggested classification.

# Filter improvements: Gene and allele ratio

The filter settings now allows using genes as a variable in rules for filters or exceptions. This allows conditioning any rule on the presence/absence of a gene, e.g. exclude certain genes from a particular filter.

In addition, it is now also possible to use allele ratio (alternative allele reads/total reads) as a variable in the quality filter. In our experience, this gives a more powerful filter than using the qual variable, especially for high sequencing depths. A caveat is that mosaic variants may be missed, but this can be partially be circumvented by adding particular genes where mosaics are expected to a gene exclusion rule as described above.

# All changes

# Version 1.7

Release date: 05.09.2019

# Highlights

# Improved import

Import of variants in various text formats and ordering of reanalyses from existing samples is now merged into a single import section on the OVERVIEW page, replacing the old IMPORT button in the top bar.

The new import solution includes the possibility to adjust the priority (for the OVERVIEW work lists) for any import involving a sample. In addition, it is now possible to search for multiple genes at once (batch query) when ordering a custom reanalysis, e.g. by pasting a list of genes from an external source. Both gene names and HGNC ID is supported, and any genes not found are shown as a list that can be copied out.

Figure: The new batch filter mode for searching for multiple genes when ordering a custom reanalysis.

# Gene panel info

Various information about the gene panel used in an analysis is now available via a new button in the top bar:

The information includes which genes are in the panel (with inheritance and default transcript available on mouse-over; list can be copied), as well as a list of the five most similar gene panels:

Figure: Gene panel info.

# Improvements to attachments

Attachments are now named after the filename (instead of an index number), and details are available by hovering the mouse over an attachment.

# All changes

# Version 1.6.2

Release date: 09.08.2019

# Fixes

  • Fixed performance bug that caused excessive loading time for ANALYSES overview.

# Version 1.6.1

Release date: 27.06.2019

# Fixes

  • Fixed add/remove buttons for variants not working in REPORT side bar.

# Version 1.6

Release date: 16.06.2019

# Highlights

This update brings a few improvements to the user interface and workflow, in addition to several bug fixes.

# Quick check boxes for BS1/BS2 and ACMG indicators

The most noticeable changes are the addition of selection buttons for ACMG criteria BS1 and BS2 (and shortened button titles) in the QUICK CLASSIFICATION mode, and addition of indicators for added ACMG criteria in the side bar.

Note that to select CLASS 2 for a variant in QUICK CLASSIFICATION mode, you must now first add at least one benign ACMG criterion (e.g. BS1/BS2 via the check boxes); see the figure below.

Figure: Check boxes for BS1 and BS2 for CLASS 2, and ACMG indicators (vertical bars next to CLASS column) in side bar.

# Outdated variants treated as UNCLASSIFIED

This update also brings a few changes to how outdated variant interpretations are handled. These are now grouped with UNCLASSIFIED variants in the side bar of an analysis, and must be reopened individually by clicking the RE-EVALUATE button if a new evaluation is to be made. This is to ensure a new validity period is only set for variants that have actually been re-evaluated.

As an added measure, the classification of reopened variants must also be actively reselected.

# All changes

# Version 1.5

Release date: 23.05.2019

# Highlights

# Classification view modes

The VISUALIZATION page has been redefined as a view mode on the CLASSIFICATION page, allowing for easier switching between relevant views while performing variant classification. Switching between view modes can now be done with three buttons above the variant list in the side bar:

  • FULL (new button; default view mode).
  • VISUAL (renamed from VISUALIZATION; button moved from top bar).

# Changes to side bar functionality

It is now possible to mark variants as TECHNICAL in the side bar in VISUAL mode (with commenting after marking, similar to QUICK mode), and the INDICATIONS COMMENT from the REPORT page is mirrored in the side bar on the CLASSIFICATION page, allowing for a more efficient workflow.

# ACMG modified criteria according to ClinGen

ACMG criteria where the strength of the original criterion are now displayed according to ClinGen's recommendations, e.g. PM1_Strong instead of PSxPM1.

# All changes

# Version 1.4.1

Release date: 15.04.2019

# Additions and fixes

  • Increase overview update interval to lessen strain server.
  • Fix automatic import of analyses with underscore in the gene panel name.
  • Fix issue where finalization would not work under certain conditions.

# Version 1.4

Release date: 26.03.2019

# Highlights

# Variant filter configurations

ELLA now supports configuring several filter configurations for a user group. This lets you define filter chains that are specific to certain types of analyses (e.g. single or trio analyses) or specific analysis names. One analysis can have several applicable filter configurations which will show up as options in the side bar inside the analysis workflow:

Figure: Switch between different filter configurations in an ongoing analysis.

Examples of possible filter configurations are different levels of frequency thresholds, or being able to turn on and off family (segregation) filtering for an analysis.

# New variant filters

Current filters include:

  • Classification filter
  • Consequence filter
  • External filter
  • Frequency filter
  • Inheritance model filter
  • Polypyrimidine filter
  • Quality filter
  • Region filter
  • Segregation filter

See new section Concepts/Filters in the documentation for details on how these filters work and how to configure them.

# Comment editor additions

The comment editor now supports inserting pre-defined templates, as well as references from the STUDIES & REFERENCES section, using two new buttons in the comment field menu. Templates can be defined independently for different comment fields, and supports basic text formatting.

Figure: Adding templates and references.

If no template has been defined or no reference has been found/added (STUDIES & REFERENCES section), the respective buttons will be inactive (greyed out).

# New features

# Other additions and fixes

  • Added ADD STUDIES button in top bar.
  • Fixed description for ACMG criterion BP6.
  • Fixed missing scrolling in "Show analyses".
  • "PL" removed from Quality card in ANALYSIS SPECIFIC section.
  • Changed order of sections on CLASSIFICATION page to PREDICTION - EXTERNAL - STUDIES & REFERENCES
  • References are now ordered (descending) according to publication year.
  • Changed colour of O tag in side bar.

# Backend

  • Added broadcast functionality to convey important messages in ELLA to all users.
  • Improvements to filter efficiency and speed.

# Version 1.3.1

Release date: 21.12.2018

# Additions and fixes

  • Fix issue in Variant report when parsing warning from pipeline, in some cases yielding wrong number of poorly covered regions.

# Version 1.3

Release date: 14.11.2018

# Highlights

# Visualization (analysis workflow)

As part of this release, igv.js (opens new window) has been integrated into ELLA as part of a new visualization feature. ELLA now let's you visualize all variants in an analysis, along with user customizable tracks at three different levels: global (all users), user group and analysis.

ELLA provides a few special tracks by default:

  • Gene panel: Shows the analysis' gene panel.
  • Classifications: Shows all classifications present in the database.
  • Variants: Shows the analysis variants after filtering.

Figure: New visualization feature.

# Mark "Not relevant" (analysis workflow)

Variants can now be marked as Not relevant for the analysis. Such variants can, depending on the user's configuration, be left without a selected class upon finalization of the analysis.

# Quick classification (analysis workflow)

A new quick classification view is now available, aimed at certain workflows for large analyses with many variants. It gives a summary of the most important information necessary for classifying variants as Technical, Not relevant or Class 2.

It is most relevant for workflows where you first perform a quicker interpretation of certain variants, before doing a more thorough interpretation of the remaining ones.

Figure: Quick classification view.

# QUALITY card renamed to ANALYSIS SPECIFIC (analysis workflow)

The card in Classification view previously referred to as QUALITY is now called ANALYSIS SPECIFIC to highlight the fact that it's not part of a variant's classification, but rather just a part of the analysis.

The card is blue and collapsed by default, to further separate it from the classification related cards.

# Improved view of existing and current class in sidebar (analysis workflow)

The view of a variant's class in the sidebar has been improved.

Left number is existing class, right is new. An arrow indicates that a new classification will be created. Blue background indicates that the variant has been reviewed. You can toggle the review status by clicking on the class in the sidebar.

# New user manual

A new, online user manual is now available from within ELLA itself. You can access it by clicking Documentation in the top navigation bar in the overview.

# New features

# Other additions and fixes

  • Filtered variants are now shown as a list (analysis workflow).
  • QUALITY card is renamed to ANALYSIS SPECIFIC (analysis workflow).
  • Improved view of class in sidebar (analysis workflow).
  • Workflows can now be finalized with technical, not relevant and/or missing classifications (depending on configuration). Workflows can still force valid classifications for all variants if desired (old behavior). (analysis workflow)
  • Requested date is now read from input .analysis file and used in overview.
  • Too wide images in comments will not make the page scrollable in the horizontal direction.
  • Overview comment is now visible for Finalised analyses and variants in overview.
  • Low quality warning is removed for Sanger variants, as there is no quality data.
  • HTML content is now properly sanitized when pasted into comment fields.
  • Fix issue where technical status was not reflected in the TECHNICAL button in the QUALITY card under certain conditions.
  • Fix issue where image could not be resized in reference evaluation.

# Version 1.2

Release date: 02.10.2018

# Highlights

# Family analysis

ELLA now lets you interpret analyses with variants that have been joint called within a single family.

The following segregation models are supported:

  • De novo
  • Autosomal recessive homozygous
  • X-linked recessive
  • Compound heterozygous

The most powerful filtering requires two parents to be present in the analysis, but some segregation filters and tags also apply to analyses with only siblings (unaffected and/or affected).

Figure: Segregation tags in sidebar.

Variants filtered out by these filters can be found in the Segregation category in the excluded variants.

# Work log

The analysis and variant workflows now have their own Work log. The work log currently lets you:

  • Update the Overview comment (previously Review comment)
  • Clear any analysis warnings (analysis only). Clearing a warning makes the warning tag disappear from the Overview.
  • Adjust the priority of the analysis or variant
  • Add messages that should be available to yourself or later interpreters about things that are relevant for the interpretation of the analysis or variant. Messages can contain formatting and images, and are editable until the next interpretation round is started.

All options in the work log can be changed at any time, without having to start a new interpretation round.

Figure: Work log example.

If there are any messages since last time the workflow was Finalised, the work log button will appear in purple, along with the current message count.

Figure: 2 messages since beginning or last finalization.

# Variant warnings

Variants are now tagged with warnings whenever there is something special that considered for the variant in question. The list of warnings will be expanded later, but currently includes:

  • Worse consequences in other transcripts
  • Other variants are within 3 bp of the variant in the analysis

Variant warnings are implemented for both the variant and analysis workflows, but some warnings are only available for analyses.

Figure: Example warning.

Figure: Warning tags in sidebar.

# New features

# Other additions and fixes

  • Quality is now it's own section in Classification view (analysis only)
  • Quality verification for variants in an analysis (Verified and Technical) is moved from the Info view to the Quality section in the Classification view.
  • Variants marked as Technical are moved to it's own list in the sidebar.
  • Improvements in display of variants with multiple selected transcripts.

# Version 1.1.2

Release date: 18.07.2018

# Additions and fixes

  • Add red 'HOM' tag to top variant bar in order to improve homozygous visibility.
  • Merge utr and intron filters into a new, improved region filter.
  • Improve search performance (entering a gene is now required for searches using HGVS nomenclature).
  • Show more information about the available samples in import view
  • Add new external database for gene TP53
  • Fix missing Hemi total count for gnomAD

# Version 1.1.1

Release date: 24.05.2018

# Additions and fixes

  • Add BRCA Exchange to external databases for BRCA1 and BRCA2
  • Add ability to search using genomic position on format g.123456
  • Keep existing reference evaluation data when clicking 'Ignore'
  • Fix link and reference description in reference evaluation window.
  • Fix issue where some variants would appear with two gene panels in variants overview
  • Fix issue where worst consequence would not display correctly for a rare case with variant having intron_variant as consequence in one transcript and splice_region_variant, intron_variant as consequences in another transcript.
  • Fix issue importing Pubmed XML data for some references.

# Version 1.1

Release date: 15.05.2018

# Highlights

# New import functionality

Requires access to the import view.

ELLA now lets you re-import previously run samples, using either an existing gene panel or a gene panel customized for that specific sample.

This lets you request new analyses directly in the application and shortens the time for reanalysis with a different set of genes.

# Frontend code improvements

The frontend code has been refactored to make it more responsive and to make it easier to add new functionality going forward.

# Other additions and fixes

  • Display number of excluded references on 'SHOW EXCLUDED' button
  • Remove scrollbar on comment fields.
  • When there are multiple transcripts in a gene panel, sort them by name. Also display all transcripts in more places, for example in the variants overview.
  • Do not add references with Relevance: 'No' to the excluded references list.
  • The 'ADD EXCLUDED' window for adding excluded variants now loads faster.
  • Search results will now show correctly when typing quickly.
  • Many other smaller UI fixes
Last Updated: 12/18/2020, 10:03:27 PM