Software release notes

New features:

• Support for new software application: QCI Analyze 1.5.0

Configuration upgrades:

• Configuration data (applications and tests) for GeneRead QIAact AIT DNA UMI panel have been added.

Analysis workflow updates

• New AIT UMI FFPE analysis workflow providing secondary analysis for the GeneRead QIAact AIT DNA UMI Panel on FFPE samples.
• Name changes:
  • The AIT FFPE and AIT Plasma analysis workflows have been renamed AIT Basic FFPE and AIT Basic Plasma, respectively.
  • The BRCA 1/2 FFPE analysis workflow has been renamed to BRCA 1/2 Basic FFPE.
• AIT Basic FFPE and Plasma analysis workflows - updated Variants of Interest (VOI) replacing 'N' alleles by the three appropriate variant alleles. This does not impact variant calling but ensures correct VOI annotation in variant tables. A total of 5 positions were updated; 2 in NRAS, 3 in ALK.
• Configuration of quality control criteria: It is now possible to modify quality control criteria for analysis workflows.

New features and improvements

• User interface styling and feature upgrade, including:
  • Relocation of Logout to bottom of user interface.
  • New Help dialog provides links to user manual and contact support details<.li>
  • New About dialog features End User License Agreement.
• BAM export: It is now possible to export .BAM and .BAI files for sample analysis derived from DNA panels.
• Additional reviewer indication and notification: When you open an analysis report, a pop-up dialog will notify you if the report is already being reviewed by someone. Likewise, the person viewing the report will be notified that you are opening it. Additionally, a vertical blue line on the analysis report tab will indicate that others are viewing the report.
• Bulk start of analysis: When starting analyses manually, the same analysis workflow can now be applied to multiple sample analyses at the same time.

New Configuration page for administrator users

• Easy overview and access to configuration of analysis workflow parameters, including quality control criteria
• New 'reset to default' button allows user to reset all parameters for a particular analysis workflow to default values
• It is now possible to modify QCI Interpret upload specifics for analysis workflows, including which QCI Interpret pipeline sample analysis results should be uploaded to.

Administrator page

• QCI Interpret connection is now readily configured from within the administrator page user interface.
• Additional analysis workflows can be easily installed and uninstalled by clicking the 'Install from file' and 'Uninstall' buttons.
• New improved user and group administration.

Comparison

• New comparison tool for validation support: Benchmark analysis results lets you compare results from one or more analysis workflows to your gold standard VCF and as such can assist in validation of analysis results. The HTML report features a track viewer for easy inspection of the relevant read mappings.
• Compare analysis results:
  • Renamed, was previously called Comparison of QC and Variants.
  • Now supports comparisons of CNV and fusion results.
• General improvements to the comparison report including upgrades of legends, inclusion of additional columns and info.
• Comparison overview:       
  • Comparisons are now listed as links like regular analysis reports.
  • Information about the Analysis workflow is now listed.
  • Delete: It is now possible to delete a comparison report.

Sample analysis details panel

• ‘Being reviewed by’ entry indicates if another user is reviewing the analysis result.
• Log entries are now listed in the details panel.
• Failed analysis can now easily be re-queued by pressing the Rerun option.

Sample analysis report

• Legends can now be expanded and collapsed.
• Summary - full summary of analysis results, same as what is presented in the Analyses overview details panel.
• Quality Control – introduction of ‘median coverage in target regions’ to QC table 2.2.
• Variants - Bulk variant editing: It is now possible to edit and move multiple variants in one go.
• CNVs - CNV reporting now specifically calls out if CNVs cannot be assessed for one or more genes, e.g. due to low global sample coverage.
• Fusion graphics - the fusion report now includes a graphical representation of fusions present in a sample.
• Detailed QC tab general overhaul.
• Track viewer - Improved visualization of <1% VAF insertions: The Genome browser now shows insert bases and reference gap for all reported and detected insertions. Previously, insertions below 1% variant allele frequency were collapsed and indicated only by a vertical line in reads..

QCI Interpret for GeneReader integration

• Improved QCI Interpret for GeneReader integration to ensure a more seamless upload. QCI Interpret for GeneReader users are now automatically authenticated when logging into QCI Analyze. This eliminates the need for separate QCI Interpret for GeneReader login when uploading samples. When pressing upload, the QCI Interpret interview page opens in new browser tab.
• Upload to QCI Interpret for GeneReader China is now supported.
• QCI Interpret for GeneReader Test Product Profiles are now supported and can be configured on a per analysis workflow basis from the QCI Analyze Configuration page.

Bug fixes

• Lung Fusion: Fixed an issue where for Lung Fusion analysis workflows the DNA contamination value would be displayed at a factor 100 too big.
• Comparison: Fixed an issue, in which if samples contained more than 2.1 billion nucleotides the median calculated in the "Comparison of QC and Variants" comparison report could be reported as a negative number.
• Track viewer: Fixed an issue where at certain zoom levels the track viewer ideogram would lose its genes if the user changed to a different report tab and back.
• GeneReader Planner: Fixed a misalignment between GeneReader Planner and the GeneReader; flow cell names now no longer can contain a "." in the GeneReader Planner.
• Data clean-up: Fixed an issue in which the data associated with a sample was not always completely cleaned up when the sample was archived.

Known issues

• Qual value missing for some variants
  Description: In rare cases the variant Qual value cannot be calculated due to an underlying issue. Such variants will appear in the QCI Analyze variant tables with an empty Qual field. The underlying NaN value is visible from the track viewer pop-up info box. We are working to address this in a future version.
• For genes on the positive strand, variant coding impact for duplications of intron-exon splice sites may be wrong
  Description: Genomic duplications of the intron-exon splice site - an event that effectively adds bases to the exon codon region and thus changes the amino acid sequence - will be reported in QCI Analyze as an insertion. As insertions in QCI Analyze by default are left-aligned relative to the reference genome, for genes on the positive strand the duplication can, in rare cases, be attributed to the intro and consequently, the mutation will be reported incorrectly as having no amino acid impact. For genes on the negative strand, the duplication will be attributed to the exon, and the corresponding amino acid impact correctly assigned.
  Based on the QIAGEN Knowledgebase, we could identify the following pathogenic variants in BRCA2 associated with hereditary breast cancer:
  
  
  • BRCA2 p.A2603Gfs*46
  • BRCA2 p.Asn2879Lysfs
  
  Pathogenic variants in somatic cancer, which are affected by this issue, could not be identified for the current GeneReader QIAact panels and therefore the risk that this issue will have an impact for you is very small.
  
  How to identify potentially affected variants:
  1. In the variant table column 'Type', look for 'insertions'. Select the 'Filter' item to access the 'Advanced Filter' and filter for ‘Type/contains/Insertion’.
  2. Look for variants with no p. variant annotation (indicating placement in non-coding area). Sort by clicking the column header.
  3. In the column ‘c. variant’, look for annotations signifying placement in the 3’ end of an intron. The format will be ‘c.ex-in’, ‘ex’ and ‘in’ being digits (e.g. c.88-3). ‘ex’ indicates the first position in the downstream exon, ‘-‘ (minus) that the insertion is placed 5’ of this exon, and ‘in’ the position in the intron measured from the splice site. Use the Advanced Filter to filter for ‘c.variant/contains/-‘. If any variants remain, inspect the ‘in’ digit. Only variants for which ‘in’ is smaller than the length of the insertion will potentially be affected by this issue.
  4. Check to see if the variant is located in a gene on the positive strand. Select the variant and inspect the blue gene annotation bar in the right-hand side track viewer. Zoom out to view the full gene. If located on the positive strand, the gene annotation bar will point to the right. If a variant is located in a negative strand gene it will not be affected by this issue.
  
  For variants which, based on the above, are flagged as potentially affected by this issue, check the read mapping to determine if the insertion is in fact a duplication covering the intron-exon splice site. If so, note that this variant will in fact give rise to amino acid changes and should be considered for downstream interpretation.