Omixon HLA Twin™ | NGS for HLA Genotyping & Ion Torrent

Release Notes

Omixon HLA Twin CE 4.4.1

Automated analysis did not start:
- Fixed, 4.4.1 handles multi level folder structures correctly. Now it starts after recognizing the automation task
Missing genotype tree on the Genotyping Sample result screen:
- Fixed, visible on the screen
Visualization errors caused by Novelties:
- Fixed, every visualization mode is available in case of Novelties.
Missed novel alleles in rare cases in Omixon HLA Twin 4.x.x:
- Fixed, again correctly called
Updated third party software component (Spring framework) to the most recent version
Product Info page update: CE, IVD and IFU logos added
Twin User guide: CE and IVD logos added to Cover page

Omixon HLA Twin RUO 4.4.1

Automated analysis did not start:
- Fixed, 4.4.1 handles multi level folder structures correctly. Now it starts after recognizing the automation task
Missing genotype tree on the Genotyping Sample result screen:
- Fixed, visible on the screen
Visualization errors caused by Novelties:
- Fixed, every visualization mode is available in case of Novelties.
Missed novel alleles in rare cases in Omixon HLA Twin 4.x.x:
- Fixed, again correctly called
Updated third party software component (Spring framework) to the most recent version
Product Info page update: IFU logo added

Omixon HLA Twin CE 4.4.0

New Features
- Significant performance increase, i.e. shorter analysis time. (Greatly depends on Installation mode and Hardware specifications)
- Support for the latest IMGT database versions (3.40, 3.41, 3.42).
- New Assay version support (OmniType)
- File Search
  File Search is a free text search that allows locating sample (fastq) and analysis (htr) files based on the file name across the database of HLA Twin. It can be accessed from any screen via the magnifying glass icon in the top left section of HLA Twin.
- Extended support of special characters in Twin
- Export P/G groups to Excel
  Table export has the new option: Export P/G groups.
- Show allele dropout in Genotyping sample results screen
  Allele dropout markup is displayed next to the locus name on the Genotype tab of the Genotyping sample result screen
- Display homozygous typings blue in Genotyping sample result screen
  Homozygous allele names are displayed in blue on the Genotyping sample result screen
- XLS table export format is replaced by XLSX
  XLS report is not supported in HLA Twin 4.0+ as the XLS format has a row limit of 65536 and column limit of 256 which makes it impossible to export Result files with 11 loci
- Extended mismatch view modes in Gene Browser
  Three state switch (Ctrl+D) cycles between the following states: 1. All visible, 2. All difference colored (previous highlight mode), 3. Mismatches colored only

Improvements and Bug Fixes
- HPRIM - line break before caret
  HPRIM standard mandates new lines to be replaced by the caret (^) character in comment lines. The previous implementation did not take different newline encoding across the various platforms. This implementation fixes this problem.
- HPRIM - Ambiguity comment issue
  Ambiguities were exported falsely to HPRIM due to the incorrect use of "/" and "+" delimiters. Expected behaviour: C|1||06:02/06:116N + 16:02 vs. Wrong behaviour: C|1||06:02/16:02 + 06:116N/16:02
- Improved Result Accuracy
- Software speedup in Sample Result screen, Genome browser
- PDF export shows 4 fields precision in case of statistical analysis with 3 fields only
- Hemizygous alleles assigned export fixed
- "N" mark is missing in HML export fixed
- L, Q, S markups are not exported in HML and PDF export fixed
- Large amount of result file opening could cause system slowing even crash
- Genotyping Dashboard visualization fixes
- Error popup on startup crash/issues
  Error popup is displayed when the startup fails, detailing the reason (OpenGL not available, MySQL not running, etc.)
- Restore the ability to add allele of alternative algorithm in the Gene browser
  The function "Add allele of alternative algorithm" is available again in the Gene browser as a context menu function
- Disable assignment button in Ready and Approved states
  Assignment buttons are disabled in Ready and Approved states
- Best match markup is shown for custom alleles in loci with no allele call
  Falsely best match markup was displayed for custom added alleles to consensus sequences in loci with no allele call. This is now fixed and custom alleles will not have any markup by default before the allele name
- Assigned null allele from HLA-DRB4 is missing from the PDF: HLA genotyping result section
  PDF export of HLA-DRB4 01:03:01:02N allele is corrected
- Improved SG configuration
  Parameters of the Statistical Genotyping have been optimized for the improved performance
- DPB1 ambiguity report correction
- Export Results - export fails when the target folder is not existing
  Export target folder check is implemented. If the target folder is non-existent the user is warned and provided with the options to create a new folder or choose a different target folder.
- Genotyping of single read samples causes TWIN to hang. Twin has to be restarted to be able to execute new analysis.
  Genotyping of single read samples won`t cause TWIN to hang anymore
- HML export - "Remove novelty marks" option is not working
  HML export always contained novelty marks, even when “Exclude novelty marks” was selected
- XLSX export on Genotyping sample result screen/Show Novelties/Export Results is now working as expected
- Unassigning one allele on the Genotyping analysis result screen causes unassignment for all the assigned alleles on the same locus.
- Allele is not exported into PDF when the "Allele is known to drop out" markup appears
- Factory default analysis protocol templates are stored in a config file instead of the database
- Missing comment button in Genotyping Results View in case of novel alleles
- Simplified installer version (migration option removed as well)
- Various improvements and bugfixes

Omixon HLA Twin RUO 4.4.0

New Features
- Significant performance increase, i.e. shorter analysis time. (Greatly depends on Installation mode and Hardware specifications)
- Support for the latest IMGT database versions (3.40, 3.41, 3.42).
- File Search
  File Search is a free text search that allows locating sample (fastq) and analysis (htr) files based on the file name across the database of HLA Twin. It can be accessed from any screen via the magnifying glass icon in the top left section of HLA Twin.
- Extended support of special characters in Twin
- Export P/G groups to Excel
  Table export has the new option: Export P/G groups.
- Show allele dropout in Genotyping sample results screen
  Allele dropout markup is displayed next to the locus name on the Genotype tab of the Genotyping sample result screen
- Display homozygous typings blue in Genotyping sample result screen
  Homozygous allele names are displayed in blue on the Genotyping sample result screen
- XLS table export format is replaced by XLSX
  XLS report is not supported in HLA Twin 4.0+ as the XLS format has a row limit of 65536 and column limit of 256 which makes it impossible to export Result files with 11 loci
- Extended mismatch view modes in Gene Browser
  Three state switch (Ctrl+D) cycles between the following states: 1. All visible, 2. All difference colored (previous highlight mode), 3. Mismatches colored only

Improvements and Bug Fixes
- Error popup on startup crash/issues
  Error popup is displayed when the startup fails, detailing the reason (OpenGL not available, MySQL not running, etc.)
- Restore the ability to add allele of alternative algorithm in the Gene browser
  The funcion "Add allele of alternative algorithm" is available again in the Gene browser as a context menu function
- Disable assignment button in Ready and Approved states
  Assignment buttons are disabled in Ready and Approved states
- Best match markup is shown for custom alleles in loci with no allele call
  Falsely best match markup was displayed for custom added alleles to consensus sequences in loci with no allele call. This is now fixed and custom alleles will not have any markup by default before the allele name
- Assigned null allele from HLA-DRB4 is missing from the PDF: HLA genotyping result section
  PDF export of HLA-DRB4 01:03:01:02N allele is corrected
- Improved SG configuration
  Parameters of the Statistical Genotyping have been optimized for the improved performance
- DPB1 ambiguity report correction
- Export Results - export fails when the target folder is not existing
  Export target folder check is implemented. If the target folder is non-existent the user is warned and provided with the options to create a new folder or choose a different target folder.
- Genotyping of single read samples causes TWIN to hang. Twin has to be restarted to be able to execute new analysis.
  Genotyping of single read samples won`t cause TWIN to hang anymore
- HML export - "Remove novelty marks" option is not working
  HML export always contained novelty marks, even when “Exclude novelty marks” was selected
- XLSX export on Genotyping sample result screen/Show Novelties/Export Results is now working as expected
- Unassigning one allele on the Genotyping analysis result screen causes unassignment for all the assigned alleles on the same locus.
- Allele is not exported into PDF when the "Allele is known to drop out" markup appears
- Factory default analysis protocol templates are stored in a config file instead of the database
- Missing comment button in Genotyping Results View in case of novel alleles
- Various improvements and bugfixes

Omixon HLA Twin RUO 4.3.0

Improvements:
- Result accuracy improvement
- New assay version supported (OmniType)
- Simplified installer version (migration option removed as well)
- Software speedup in Sample Result screen, Genome browser
Export bugs fixed:
- PDF export shows 4 fields precision in case of statistical analysis with 3 fields only
- Hemizygous alleles assigned export fixed
- "N" mark is missing in HML export fixed
- L, Q, S markups are not exported in HML and PDF export fixed
Behavior bugs fixed:
- Large amount of result file opening could cause system slowing even crash
- Genotyping Dashboard visualization fixes

Omixon HLA Twin CE 4.2.2 (Windows only!)

HPRIM Export related fixes and improvements

Omixon HLA Twin CE 4.2.0

Up to 70% analysis speed improvement with "Fast mode"
Analysis speed is almost independent of the size of the IMGT/HLA reference database
Result file (HTR) sizes reduced by several magnitudes (from up to gigabytes to tens of megabytes per
result file), thus reducing long-term data storage requirements significantly
Minor update to the latest supported IMGT/HLA reference database (version 3.38.0_9) to support fast mode
Analysis failures with reference database IMGT/HLA 3.38.0 have been resolved
Export bug fixed: issue with exporting P and G group precision in HML and PDF is resolved
Export bug fixed: assigned hemizygous alleles are now exported properly
GUI bug fixed: the reference database update window is now handled properly
Behavior improvement: the HLA Twin Server application with an incorrect IP address can be successfully terminated
Behavior bug fixed: the sample files were registered incorrectly in special cases
HPRIM bug fixed: homozygous novelties are now reported correctly
HPRIM bug fixed: novelties are now named properly on the 4th field
HPRIM bug fixed: hemizygous alleles are now exported properly
HPRIM bug fixed: only the last comment is now exported as opposed to the full comment history
HPRIM improvement: comments now comply with customer specifications

Omixon HLA Twin RUO 4.2.0

Up to 70% analysis speed improvement with "Fast mode"
Analysis speed is almost independent of the size of the IMGT/HLA reference database
Result file (HTR) sizes reduced by several magnitudes (from up to gigabytes to tens of megabytes per
result file), thus reducing long-term data storage requirements significantly
Minor update to the latest supported IMGT/HLA reference database (version 3.38.0_9) to support fast mode
Analysis failures with reference database IMGT/HLA 3.38.0 have been resolved
Export bug fixed: issue with exporting P and G group precision in HML and PDF is resolved
Export bug fixed: assigned hemizygous alleles are now exported properly
GUI bug fixed: the reference database update window is now handled properly
Behavior improvement: the HLA Twin Server application with an incorrect IP address can be successfully terminated
Behavior bug fixed: the sample files were registered incorrectly in special cases

Omixon HLA Twin CE 4.1.0

The software has gone through a major overhaul providing a more responsive and comfortable experience. This includes:

New features:

Serological equivalents and Bw4/Bw6 reporting for allele pairs
New novel allele export feature with table file export for easier submission of novel alleles to GeneBank and IMGT
PIRCHE epitope matching integration
Sample files now can be sorted by their sample/index number (S1, S2, etc...)
A new Typer Scheduler window was introduced that allows the user to change the order of scheduled analyses of samples

Improvements:

Algorithmic tweaks providing about 25% faster analysis time per sample
A more robust database solution for better performance (MySQL)
Faster folder loading
Better response times between folders and screens
Improved and more reliable server-client connection
An improved automated analysis method
The Genotyping analysis result and Genotyping sample result screens were redesigned for more intuitive display of results, especially designed to handle the increasing the 4th field ambiguity rates caused by the expanding IMGT database
New distributed typer scheme

Bug fixes:

Memory-related issues which caused the server to crash have been fixed
HPRIM export-related issues have been fixed
"Too ambiguous to report" message in the PDF export has been removed and an extended number of allele pairs are listed instead
A bug where specific DQB1 alleles were not viewable in the Genome browser has been fixed

Omixon HLA Twin RUO 4.1.0

Improvements and fixes:

Algorithmic tweaks providing about 25% faster analysis times per sample
Approved results can be exported successfully
The Setup Loci options now will not change automatically

New features:

Serological equivalents and Bw4/Bw6 reporting for allele pairs
New novel allele export feature with table file export for easier submission of novel alleles
Sample files now can be sorted by their sample number (S1, S2, etc...)

Omixon HLA Twin RUO 4.0.1

Improvements and fixes:

A more reliable database solution was implemented
The logic behind the automated analysis was improved
Bugs in the genotyping dashboard were fixed
Minor problems with the installer were fixed

Omixon HLA Twin RUO 4.0.0

New features:

Automated analysis support for the new Illumina Local Run Manager software running on MiSeq and MiniSeq sequencers

Other technical improvements and fixes:

New user interface layout with improved response times
A new and more robust distributed typer configuration
The order of the samples scheduled for analysis can be rearranged
External SQL database support
New licensing system

Omixon HLA Twin RUO 3.1.3

New features:

PIRCHE epitope matching integration

Other technical improvements and fixes:

Reporting and genotyping performance improvement when using remote work folder

Omixon HLA Twin CE 3.1.1

New features:

V3.0 assay support
ABO and MICA genotyping support
New allele database structure and format
New QC metric to assess the number of novel positions

Other technical improvements and fixes:

Overall faster response between pages
Sample folder loading speed-up
Memory handling refinements and improvements
Increased stability when more read data is analyzed
Temporary folder cleanup refinement
Exporting related fixes and improvements

Omixon HLA Twin RUO 3.1.1

New feature:

New QC metric to assess the number of novel positions

Other technical improvements and fixes:

Overall faster response between pages
Memory handling refinements and improvements
Exporting related fixes and improvements

Omixon HLA Twin RUO 3.1.0

User interface performance improvements:

Overall faster response between pages
Sample folder loading speed-up

Other technical improvements:

Memory leak patch
Memory handling scheme change
Increased stability when more read data is analyzed
Temporary file cleanup refinement

Omixon HLA Twin RUO 3.0.0

V3.0 assay support
Whole gene analysis for Statistical Genotyping
ABO and MICA genotyping support
New allele database structure and format

Omixon HLA Twin CE/RUO 2.5.1

Spot noise ratio calculation redefined.
Spot noise ration thresholds were refined.
Improved client response in server-client installations.
Minor refinements in HPRIM export format.

Omixon HLA Twin CE/RUO 2.5.0

New features and improvements

Holotype HLA v2 kit support: Assay version selector allows user to select the right assay version for analysis.
IMGT/HLA 3.29.0.1_5 database version was released:
- HLA-DRB1*09:01:02 allele extension was removed
- Erroneous HLA-DRB1*14:13 allele sequence was replaced with record from IMGT/HLA 3.30.0
- The database was validated with the following software versions: Omixon HLA Twin 2.1.3 CE & RUO, Omixon HLA Twin 2.1.4 CE & RUO and Omixon HLA Twin 2.5.0 RUO. For other software versions, each laboratory is advised to do its own internal validation.
Distributed typing service allows for batch analysis and filtering tasks to run in parallel in a client-server environment
Existing user accounts cannot be deleted through the UI; administrators have the option to disable and reactivate them whenever needed
New export options:
- JSON export for result files
- Fasta export for consensus sequences
- Export result files to PDF/HML with or without LD data
Re-Analyse button for result files added
Improved automated analysis options: predefined time values for triggering analysis
File system access rights are now considered on the HLA Typing dashboard: inaccessible folders are marked red and cannot be clicked
Pause/resume option for analysis tasks was removed from client-server installations
Improved “Targeted Gene List” loading when configuring analysis

Bugfixes

Algorithm improvement to fix reported false allele calls
Spot noise calculation was fixed for reported special cases
Temporary file cleanup fix to avoid losing files still in use
Fix for inconsistent display of missing genotype markups
Amino acid track fixes for special cases
HML export fix: best matching alleles are always exported now
Genome browser bug resulting in "rainbow effect"
Continuous consensus QC metric corrected
Bugs related to result approval were fixed:
- Commenting on approved results isn't possible any more
- Result approval buttons work consistently with all precision settings

Omixon HLA Twin RUO 2.2

Bugfixes and improvements

User details are now filled out correctly in the PDF report for results produced with automated analyses
New read mapping options introduced (skip read mapping, map reads to result alleles only or map reads to all alleles)
Read mapping information and targeted gene set added to analysis tooltips on the HLA typing dashboard
Imbalanced best matching allele results produced by a statistical-only analysis are now shown correctly
New hydrophobicity based color scheme for the amino acid track in the HLA browser
HLA browser now jumps to the first best matching pair instead of the first allele pair
Error details can now be copied to the clipboard from the task manager
Application settings dashboard side panel reorganized

Compatibility

Analysis results produced with a software version 2.2.0 or higher cannot be viewed in the genome browser with software versions prior to v2.2.0.

Performance

The following genotyping performance improvements were measured compared to v2.1.4:

Input data set	Benchmark result
96 samples 7 loci/300 chem.	715 -> 593 sec/sample, total 15 hours, 17% improvement
96 samples 7 loci/500 chem.	646 -> 514 sec/sample, total 12.7 hours, 21% improvement
96 samples 11 loci/300 chem.	924 -> 767 sec/sample, total 19 hours, 17% improvement
96 samples 11 loci/500 chem.	899 -> 691 sec/sample, total 17 hours, 23% improvement

Benchmarking environment:

CPU: 8 CPU - Intel(R) Quad Core(TM) i7-4770 CPU @ 3.40GHz (+all Cores are used)
Memory: 24 GB JVM heap
OS: Windows

Omixon HLA Twin RUO & CE 2.1.4

Bugfixes and improvements

QC result calculation for key exon mismatch count fixed
HML export related changes:
- Variant reporting can be turned on/off
- Novel allele postfix can be trimmed without trimming the allele name
- Export now works for newer IMGT/HLA database versions (version 3.26.0 and above)
- Novel allele postfixes are now exported correctly

Omixon HLA Twin RUO & CE 2.1.3

Improvements and bug fixes

IMGT/HLA 3.28.0 released

Omixon HLA Twin RUO 2.1.2

Improvements and bug fixes

HML export bug fixes and improvements
- New pairwise alignment base variant generation method
- Improved reference selection:
  - For not fully defined best matching alleles, the closest fully defined alleles are used as references
  - For novel allele results, the base allele is used as a reference
- Loci with no allele calls are no longer exported
Consistent naming convention for extended allele handling
Targeted locus list handling fixed in protocols
Temp folder is now created by the application if a non-existing folder was specified during installation
Null alleles and novel alleles no longer get trimmed in low resolution PDF and HML exports
Temporary file cleanup improved

Omixon HLA Twin RUO 2.1.1

Performance problem fix - Fixes the performance problems reported by some of our customers since the release of Twin 2.1.0.
Temporary folder cleanup fix - Fixes the bug where on some occasions the temporary files generated during the analyses are not deleted until the Twin Serve/Desktop is restarted, leading to excess disk space consumption.

Omixon HLA Twin RUO 2.1

HLA browser improvements
- Faster browsing - much improved loading speed of HLA browser
- Fixed some visualisation issues with misaligned exons
- Context sensitive guide for the HLA browser
Linkage Disequilibrium (LD) improvements
- Extended LD checks to cover DQB1 and DQA1 in addition to DRB3/4/5
- Fixed known display issues with DRB3/4/5 results
Improved memory settings
- On first use popup, warning if insufficient memory configured
- Recommendation for memory settings on installation
User interface performance improvement
- Faster responses from user interface when analyses are running

Omixon HLA Twin RUO 1.1.4.2

Noise filter improvements to improve genotyping results on DRB3 and DRB5
Linkage disequilibrium based result interpretation and annotation improvements
Server automation stability and performance improvements
Several other small bug fixes

Omixon HLA Twin RUO 1.1.4.1

Linkage disequilibrium based result interpretation and annotation fixes
Separated QC metrics for allele imbalance in the exon and non-exon regions
Option to add custom hemizygous genotype
Fixed HML export to consider phasing in the sequence tags
Fixed empty result presentation for loci without data
Fixed product name in the installer file name
Increased maximum memory setup limit to 512GB

Omixon HLA Twin RUO 1.1.4.0

Analysis improvements
- Resolution of DRB4*01:03:01:02N by allele database extension
- Better crossmapping detection on DRB loci
Reporting improvements
- Reporting difference between homozygous and hemizygous DRB results based on linkage disequilibrium information in publicly available databases
- Dropout cause resolution supporting hints for loci with missing genotype
- Allele frequency reporting based on the database of www.allelefrequencies.net
Usability improvements
- Notification about new IMGT/HLA database availability
- Higher quality sequence alignments in the genome browser
- Better loading performance for the genome browser
Several bug fixes

Omixon HLA Twin RUO & CE 1.1.3.4

Non-exon spot noise ratio QC metric's info threshold raised up to 20% to be not as stringent as previously
Spot noise ratio QC metric for consensus regions where no allele annotation is present in the first best allele pair is not counted from now on to be not as stringent as previously
File browser bug has been fixed for mixed Windows-Linux client-server installations
Browsing results approved with version prior to 1.1.2 has been fixed

Omixon HLA Twin RUO 1.1.3.3

New exon/non-exon spot noise ratio quality control metrics for more robust contamination detection
Minor fixes in the HML export

Omixon HLA Twin RUO 1.1.3.2

Fixed proprietary internal filtering database to improve genotyping and consensus building quality on HLA-DPA1 and HLA-DRB5
Minor fixes in the HML export

Omixon HLA Twin RUO 1.1.3.1

Upgrade installation fixes
- Fixed upgrade installation issue on Mac OS X
- Logs are no longer removed during upgrade installation
- RUO and CE cross-upgrade installation is now possible from Twin version 1.1.2
- Accidental upgrade from Twin to Explore is no longer possible
Genome browser fixes
- Multiple minor issues resolved for the variant relationship track
- Gap visualization issues corrected in the sequence displays
Logout issue when connection to server was lost has been fixed
Image display fixed in the help
Result loading performance issue has been resolved

Omixon HLA Twin RUO 1.1.3

The HLA typing software for research and discovery
- Flexible and customizable to handle various sequencing data types, i.e. targeted, whole exome or whole genome
- Includes both genotyping algorithms
Analysis improvements
- 150bp chemistry support
- Improved novel allele detection
- Better crossmapping detection
Usability improvements
- Genotype editor
- Variant phasing track in the genome browser
- Base statistics visualization in the genome browser
- Improved visibility of allele assignments
- Configurable data and result folders for better analysis result organization
- Optional secondary genotyping method execution based on QC results for performance improvement
- Scalable window contents to support very large and small resolution displays
Research use only edition - no compliance restrictions
- Custom analysis can be configured without a notification
- No audit related restrictions
Export improvements
- Optional precision reduction in the HML export
- Variant and novelty reporting in the HML export
Various usability improvements and bugfixes

HLA Twin™

HLA TWIN downloads are available for your convenience

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