Release Notes

v4.0.1

These Release Notes include new features, product limitations and known issues for Illumina Connected Insights - Research v4.0.1.

New Features

• Compatibility with DRAGEN TruSight Oncology 500 ctDNA v2.5.0 analysis software.

Defect Repairs

• 7485: Issue causing display of additional erroneous records from OncoKB on the biomarker pages for copy number gain variants (additional records are correct but associated with different variant classes).

• 7494: Issue preventing data upload in certain cases due to Alt contigs in coverage files.

• 7517: Issue preventing display of certain assertions from OncoKB on biomarker pages.

• 9411: Issue impacting display of QC metrics on the Overview page and Lab QC page in certain cases generated with the previous software versions.

• 9412: Issue impacting variant display on the Variants page in certain cases generated with the version v2.0.0.

• 9487: Sorting on the Custom Case Data page.

Known Issues

• 940: Therapy packs (e.g., Orsythia 28 Day Pack) may fail validation when adding them to an assertion.

• 1298: Read order in the BAM track may change after zooming in the IGV viewer.

• 3409: CN calls produced by DRAGEN TruSight Oncology 500 v2.5.2+ Analysis Software with CN=2 or CN > 2 and annotated as <DEL> are not displayed.

• 3594: Command Line Interface logs may take long time to sync (up to 4 hours) and not reflect latest actions if exported before the sync is completed.

• 3723: The software will display two duplicating variants if they were called by two different pipelines, for example, a small variant caller and a structural variant caller.

• 3777: Users will not be able to upload NR transcripts into My Knowledge Base. JAX-CKB assertions will not be displayed for NR transcript variants.

• 3835: Filtering for variant type “Copy Number Neutral” returns no results even if CNV with CN=2 are present.

• 3836: Biomarker page may not open and an error message “Variant not found in index” will be displayed when clicking on some events on the Genome View plot and the Variants page.

• 3934: Reopening an approved report does not trigger notification of assertion update even if there are updated assertions for the case.

• 3943: For DRAGEN RNA pipeline, RNA BAM track in IGV is not enabled by default for small variants and needs to be turned on manually.

• 5074: Copy number gain false positive findings may be presented for non-PAR chrX regions.

• 5080: A case may move to “Has issues” status if its reprocessing is ongoing on one tab and a user tries to approve the report on another browser tab.

• 5133: User preferred transcripts for a gene may not be prioritized as expected if user provides incorrect gene-transcript pairs when uploading the file with user preferred transcripts.

• 5263: A valid case can be ingested with a status “Has issues” again if it was originally ingested with “Has issues” and there was a failure with report automation.

• 5491: Coverage graph may not display findings if they use a different transcript rather than the one used to create the graph.

• 5494: In IGV, the SV variant track may show only one SV when multiple SVs are present in the same locus.

• 5599: Records from CIViC knowledge base for broad variant categories like “PTEN mutation” will match all variants for the given gene even when match is not appropriate, for example, it will match records for exon variants to intron variants.

• 6199: Data upload of analysis results generated by the DRAGEN WGS Somatic v4.2 pipeline fails when the pipeline was run on ICA starting with BAM files. A workaround is to download data locally first.

• 6200: Variant filtering based on SpliceAI score and gene name may return incorrect results due to use of different transcripts.

• 6231: Previewing Report template does not work on Safari browser.

• 6332, 6378: Fusion representation is impacted if one breakend is in chrM.

• 6584: COSMIC links for some variants lead to non-existing pages due to inconsistencies in content provided by COSMIC.

• 6623: Oncogenicity prediction tool does not correctly calculate OP3 criterion for PI3CA p.Met1? variant.

• 7241: Glioblastoma assertions on glioblastoma reports may appear in the other diseases column.

• 7284: Some recruiting clinical trials could be omitted if their status changed from “suspended” to “recruiting”.

• 7336: When assertions from multiple knowledge sources are present on different transcripts of a variant, the default transcript may not be the transcript with the highest oncogenic classification.

• 7399: In extremely rare scenarios, if a large variant or splice variant overlaps with multiple variants in another case the seen count is incremented by more than 1.

• 7429: RNA QC metrics for a merged case may not show on the Overview page in certain scenarios but are accessible from Lab QC.

• 7514a: OncoKB assertions that have “Colorectal cancer excluded” in disease name are displayed on Biomarker page, for example, a Level 1A record for BRAF V600E.

• 7514b: OncoKB assertions for colorectal cancer are not displayed on the Biomarker page when filtered for “Malignant tumor of large intestine” or other related terms. To display them, remove disease filter.

Product Limitations

• 191: The software does not yet display records related to co-occurring variants.

• 895 and 1415: The software does not consider partial exclusion criteria while listing clinical trials, for example, the trial with the following criteria will be prioritized for all listed markers “Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600), MET Exon14 skipping or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded”.

• 2489: The software fails to ingest data from network drive when data uploader utility is initiated for data ingestion on Mac computer.

• 2850, 5116, 5743: Few assertions and clinical trials from JAX-CKB for Infant-type hemispheric glioma, oligodendroglioma IDH-mutant and 1p/19q-codeleted grade 2, and oligodendroglioma IDH-mutant, 1p/19q-codeleted grade 3 and several other cancer types are not displayed in Biomarker pages.

• 3451: Assertions created for variants uploaded with GRCh37 reference genome are not displayed for the same variants uploaded with the GRCh38 reference genome.

• 6099: Unable to create assertions for extremely large copy number variants or structural variants.

• 6614: Total depth and VAF are not calculated for RNA splice variants.

v4.0.0

These Release Notes include new features, product limitations and known issues for Illumina Connected Insights - Research v4.0.0.

New Features

• Integration of OncoKB™ by Memorial Sloan Kettering Cancer Center as an additional knowledge base

• Automated oncogenicity prediction tool scoring variants to assign oncogenic, likely oncogenic, variant of unknown significance (VUS), likely benign and benign categories

• Ability to create cases (one case or a batch of cases) by uploading Case Custom Metadata file ahead of uploading secondary analysis output data

• Ability to include DNA and RNA samples into the same case using a Case Custom Metadata file if DNA and RNA secondary analysis outputs are coming from different pipelines, for example, DRAGEN TruSight Oncology 500 and DRAGEN RNA

• Total depth (a sum of paired reads and split reads for reference and alternate alleles) and VAF (a proportion of supporting reads over total depth) are now calculated for RNA fusions and structural variants

• RNA fusions and translocation structural variants are now each represented as a single record on the Overview and Variants page.

• Visualize tab in the Biomarker page to display a genome browser showing position of the variant, location of protein domains, partner and breakpoint details in case of RNA fusions and structural variants, and other information

• A plot with the number of lab’s samples including a particular variant in the Cancer Datasets section of the Biomarker page

• A separate section listing Variants of Unknown Significance (VUS) in the report template

• Audit logs accessible via API covering a comprehensive set of user actions

• Ability to upload custom annotation. Specifically, for a list of variants users can upload categorical values, numerical values and frequencies and use them for display, sorting and filtering.

• Ability to delete cases via user interface

• Links to Mastermind by Genomenon and LitVar triggering smart variant search in the Biomarker page

Defect Repairs

• 4007: Fixed an issue of updates made to case information were not reflected in the report preview page unless the preview page is refreshed. The case information appears updated in the approved report.

• 4734: Fixed an issue related to CIViC evidence for frameshift variants.

• 5617: Fixed an issue of not recognizing a gene name if a space after the gene name is entered.

• 5618: Fixed an issue related to display of fusion breakpoints in key genes on the Overview page.

• 5976: Fixed an issue of how Report Automation feature was including in reports more and less specific assertions.

• 6022: Fixed an issue of displaying Gain-of-Function (GOF) and Loss-of-Function (LOF) consequence for a variant after archiving an assertion interpreting it as GOF or LOF and updating the case.

• 6068: Fixed an issue of erroneous display of the on/off status of the Report Automation feature in older versions of Test Definitions.

• 6126: Fixed an issue of displaying a wrong user on the Configuration page for Report Automation.

• 6194: Fixed an issue of Genome Coverage graphs on the Overview page not filtering the duplicate reads.

Known Issues

• 940: Therapy packs (e.g., Orsythia 28 Day Pack) may fail validation when adding them to an assertion.

• 1298: Read order in the BAM track may change after zooming in the IGV viewer.

• 3409: CN calls produced by DRAGEN TruSight Oncology 500 v2.5.2+ Analysis Software with CN=2 or CN > 2 and annotated as <DEL> are not displayed.

• 3594: Command Line Interface logs may take long time to sync (up to 4 hours) and not reflect latest actions if exported before the sync is completed.

• 3723: The software will display two duplicating variants if they were called by two different pipelines, for example, a small variant caller and a structural variant caller.

• 3777: Users will not be able to upload NR transcripts into My Knowledge Base. JAX-CKB assertions will not be displayed for NR transcript variants.

• 3835: Filtering for variant type “Copy Number Neutral” returns no results even if CNV with CN=2 are present.

• 3836: Biomarker page may not open and an error message “Variant not found in index” will be displayed when clicking on some events on the Genome View plot and the Variants page.

• 3934: Reopening an approved report does not trigger notification of assertion update even if there are updated assertions for the case.

• 3943: For DRAGEN RNA pipeline, RNA BAM track in IGV is not enabled by default for small variants and needs to be turned on manually.

• 5074: Copy number gain false positive findings may be presented for non-PAR chrX regions.

• 5080: A case may move to “Has issues” status if its reprocessing is ongoing on one tab and a user tries to approve the report on another browser tab.

• 5133: User preferred transcripts for a gene may not be prioritized as expected if user provides incorrect gene-transcript pairs when uploading the file with user preferred transcripts.

• 5263: A valid case can be ingested with a status “Has issues” again if it was originally ingested with “Has issues” and there was a failure with report automation.

• 5491: Coverage graph may not display findings if they use a different transcript rather than the one used to create the graph.

• 5494: In IGV, the SV variant track may show only one SV when multiple SVs are present in the same locus.

• 5599: Records from CIViC knowledge base for broad variant categories like “PTEN mutation” will match all variants for the given gene even when match is not appropriate, for example, it will match records for exon variants to intron variants.

• 6199: Data upload of analysis results generated by the DRAGEN WGS Somatic v4.2 pipeline fails when the pipeline was run on ICA starting with BAM files. A workaround is to download data locally first.

• 6200: Variant filtering based on SpliceAI score and gene name may return incorrect results due to use of different transcripts.

• 6231: Previewing Report template does not work on Safari browser.

• 6332, 6378: Fusion representation is impacted if one breakend is in chrM.

• 6584: COSMIC links for some variants lead to non-existing pages due to inconsistencies in content provided by COSMIC.

• 6623: Oncogenicity prediction tool does not correctly calculate OP3 criterion for PI3CA p.Met1? variant.

• 7241: Glioblastoma assertions on glioblastoma reports may appear in the other diseases column.

• 7284: Some recruiting clinical trials could be omitted if their status changed from “suspended” to “recruiting”.

• 7336: When assertions from multiple knowledge sources are present on different transcripts of a variant, the default transcript may not be the transcript with the highest oncogenic classification.

• 7399: In extremely rare scenarios, if a large variant or splice variant overlaps with multiple variants in another case the seen count is incremented by more than 1.

• 7429: RNA QC metrics for a merged case may not show on the overview pagein certain scenarios, but are accessible from Lab QC.

Product Limitations

• 191: The software does not yet display records related to co-occurring variants.

• 895 and 1415: The software does not consider partial exclusion criteria while listing clinical trials, for example, the trial with the following criteria will be prioritized for all listed markers “Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600), MET Exon14 skipping or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded”.

• 2489: The software fails to ingest data from network drive when data uploader utility is initiated for data ingestion on Mac computer.

• 2850, 5116, 5743: Few assertions and clinical trials from JAX-CKB for Infant-type hemispheric glioma, oligodendroglioma IDH-mutant and 1p/19q-codeleted grade 2, and oligodendroglioma IDH-mutant, 1p/19q-codeleted grade 3 and several other cancer types are not displayed in Biomarker pages.

• 3451: Assertions created for variants uploaded with GRCh37 reference genome are not displayed for the same variants uploaded with the GRCh38 reference genome.

• 6099: Unable to create assertions for extremely large copy number variants or structural variants

• 6614: Total depth and VAF are not calculated for RNA splice variants

v3.0.1 (and older)

For information on new features, known issues, and bug fixes, refer to Illumina Connected Insights release notes on the Illumina support site.