Variant Analysis Release Notes

 

Release Spring

Software Version: 4.1.20160615

New Features

Ethnic group specific allele frequency information in Allele Frequency Community

In addition to variant composite frequency, users can now filter against East Asian, South Asian, African (American), European, and Hispanic sub-population frequencies in the Common Variants filter.


Compute allele frequencies from user-defined collection of samples

Empower users to establish their own “baseline” by computing frequencies based on a collection of samples (“My Libraries”), and annotating variants in a future analysis with library frequencies.

Make a copy of an existing analysis

Carry over analysis filter settings, samples, and sample metadata into a new analysis.


Improvements

  • Added back the functionality to download original VCF
  • Added OMIM gene and phenotype ID to the variants table
  • Added GQ (Genotype Quality) to the Confidence Filter and VCF export
  • Revised compound het calculation to no longer include variants of uncertain significance
  • Retain allele depth (AD) information in exported VCF if uploaded VCF specifies the field
  • Improved handling of analyses where prefiltering produce zero variants
  • Increased numerical precision to 2 decimal points for variant call quality and allele fraction fields
  • Unified syntax for Allele Frequency Community fields across application UI and exported files (now reads as “AFC frequency” or “AFC_AF”)
  • API usage of Variant Analysis Custom Pipeline will now display the entire filter cascade, rather than only variants that survived the filter

 

Ingenuity Variant Analysis version 4.1.20160615
Content versions: CGI 54 Genomes (Version2.0), SIFT (2016-02-26), EVS (ESP6500SI-V2), Allele Frequency Community (2016-06-16), JASPAR (2013-11), Ingenuity Knowledge Base (Idris 160423.001), Vista Enhancer (2012-07), BSIFT (2016-02-26), TCGA (2013-09-05), PolyPhen-2 (v2.2.2), 1000 Genome Frequency (phase3v5b), Clinvar (2016-03-01), COSMIC (v76), ExAC (0.3), HGMD (2016.1), PhyloP (2019-11), DbSNP (146), TargetScan (6.2)

 


Release Winter 2015

GRCh38/hg20 genome build support. Given increasing traction in research and clinical community adoption of GRCh38, VCF files using GRCh38 coordinates can now be analyzed in Variant Analysis. Users can annotate, filter, and compare GRCh38 samples using updated versions of public databases (1000Genomes, dbSNP, ExAC, Exome Variant Server), as well as curated content.

 Filtering speed-up. Identified filtering bottlenecks and made optimizations to reduce time needed for compute/memory intensive tasks.

Variant Analysis Release Notes

Release Fall

Whole Genome Prefilter Limit Increased from 200 to 300 Samples

To improve performance, users have the option to pre-filter their whole genome data to only exonic regions. When an analysis exceeds a certain volume of whole genome samples, pre-filtering is mandatory. With the Fall release, the upper limit that imposes mandatory prefiltering has been lifted from 200 to 300 whole genome samples. Now users performing analysis up to 300 whole genomes are not required to pre-filter. Users creating analysis with greater than 300 whole genomes must use pre-filter or contact Customer Support to create analysis without pre-filtering.

Private Control Libraries

Private Control Libraries (PCL) will allow users to compute variant frequency from a select set of samples and allow users to filter on those frequencies as well as compare case sample(s) vs all the samples in the PCL. The PCL will allow analysis with large volume of control samples to compute faster and enable much larger analysis sizes (up to 2000 whole genomes). One can also compare case(s) vs control samples within the
PCL using the Genetic Analysis and Statistical Analysis filters

The IVA application will feature a new tab “My Control Libraries” where you can see your collection of Private Control Libraries. Additionally there will be a new “New Library” button in the My Samples view to build new libraries.

When creating a new private control library, users can build a library by selecting and dragging the samples from the left pane to the right pane of the Create Control Library window.

After clicking the “Create” button, the library is processed offline and the user will be notified by email when the PCL is built. When the library is built, users can access and review the library using the My Control Libraries tab which will list all existing PCLs. From here one can edit the library’s meta data or delete the library.


Updated Build of Allele Frequency Community

The new build of the Allele Frequency Community (AFC) is based off a collection of 120,000 consented exomes and genomes. Of the 120,000 consented samples, roughly 12,000 are whole genomes and the rest are exomes.

Improved (beta) Integration with IPA™

With the Fall release, we have improved the integration between IVA and IPA. Now when you click on the Export to IPA button, IVA will export the list of gene IDs, the ACMG assessments, and the gain or loss of function information. This features is in beta and would have limited support for the Fall release.

 


 

Release Spring

Improvements to Allele Frequency Community

Allele Frequency Community members will now be able to download all the frequencies associated with the variants contained in their donated samples. This is done via the AFC Export button in the Details panel. This feature is available to all Ingenuity Variant Analysis users even unpaid users. The only requirement is that the user must opt-into the Allele Frequency Community.

Download of Raw VCF file

With the new Spring release, Ingenuity Variant Analysis users will now be able to download the raw VCF file that was uploaded to Variant Analysis. This is a great way to back up your valuable VCF files while interpreting them. Additionally core labs and commercial service providers and now use Ingenuity Variant Analysis as a way to offer their customers a delivery method for VCF files as well as NGS analysis serivces. To download the raw VCF file, simply click on the blue file name next to ‘Files’ in the details panel.

Updates to IAT

The Ingenuity Admin Tool will now feature:

The ability to see the Ingenuity Variant Analysis subscription capacity including how much free space is available

List of Group members and each members unique samples List of samples within the subscription and which group members have access to those samples. Also when adding other IVA users to the Group, the IAT will now let you know how many unique samples the new member will be bringing into the account.

PMGD Content in IVA

Ingenuity Variant Analysis users will now have access to PGMD content included with their subscription. When PGMD annotations are available for the selected variant, PGMD details may be view through the phamacogenetics link in the Details panel.

Release 3.1.20150207

Search for actionable variants in your NGS data with confidence.

This new release features access to the most extensive community database of allele frequencies, facilitated sharing, and instant access to HGMD content.

Allele Frequency Community

The Allele Frequency Community is a freely accessible “opt-in” community resource designed to facilitate sharing of anonymized, pooled allele frequency statistics among laboratories for the benefit of patients and biomedical research.  Joining the community is free.  Once you join, your NGS samples can be richly annotated with allele frequency information from the entire Community.  Non-personally identifiable statistics from community members’ samples are used to expand the diversity of the database over time.  More information about the Allele Frequency Community is available at www.allelefrequencycommunity.org

How to join the Allele Frequency Community

Ingenuity Variant Analysis users can opt their samples into the Allele Frequency Community by opting-in upon account signup,

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or clicking the new “Settings” link within Variant Analysis,

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then checking the “Contribute data …” checkbox.

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Community Allele frequencies will be available as part of the Common Variants filter, and as a column in the variants table for users who have opted-in.

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Instant Access to HGMD Content

Gain instant, direct access to HGMD content.   New in this release, users are no longer required to obtain an HGMD license from BIOBASE for access to up-to-date HGMD content.  Access HGMD content directly within Variant Analysis by clicking on a variants’ accession ID.

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Ingenuity Admin Tool (IAT) and Group Access to Variant Analysis

The IAT tool enables account administrators to easily manage group membership without contacting QIAGEN Bioinformatics Customer Support.   Users may be added or removed from your group through the Ingenuity Admin Tool (IAT) portal.   To add a group (or become a group administrator) for your subscription license, please contact Customer Support and request the addition of group access to your Variant Analysis account.

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Variant Analysis – New Purchasing Plans

Pay-by-sample plans have been eliminated in favor of a flexible tiered-based subscription model that simplifies budgeting and planning.

In October 2014, QIAGEN Bioinformatics introduced the Ingenuity Variant Analysis subscription plan.   Customers can now purchase 12-month subscriptions of Variant Analysis with the ability to select subscription tiers that correspond to their anticipated sample throughput.   Subscription tiers start at 50 samples (permitting an analysis of up to 50 samples).   For more information on the new subscription tiers please refer to the “How Variant Analysis Subscriptions Work” on the Ingenuity Variant Analysis Resources page.

Please note: Activation codes and coupons for sample activation are no longer used in subscription plans.

Content versions:

Ingenuity Variant Analysis version 3.1.20150207 Content versions: Ingenuity Knowledge Base (Dagobah 141227.000), HGMD(2014.4), COSMIC (v71), dbSNP (Build 141 (05/21/2014)), 1000 Genome Frequency (v5), TargetScan (v6.2), EVS (ESP6500 0.0.30), JASPAR (10/12/2009), PhyloP hg18 (11/2009), PhyloP hg19 (01/2009), Vista Enhancer hg18 (10/27/2007), Vista Enhancer hg19 (12/26/2010), CGI Genomes (11/2011), SIFT (01/2013), BSIFT (01/2013), TCGA (09/05/2013), PolyPhen-2 (HumVar Training set 2011_12), Clinvar (08/07/2014)

Release notes coming soon

Release 2.3.20131217

New Features/Fixes:

  • Mitochondrial variants from multiple mitochondrial reference sequences are now supported (and translated to RCRS coordinates), including genome annotations and findings, for new analyses.

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  • Sample-specific Allele Fraction can be added via Edit Columns and viewed in genotype icon tooltips for new analyses which have AD and DP variant data, to see the percentage of reads with the variant allele.

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  • Ingenuity Pathway Analysis users now get links in gene and drugs views to jump into IPA.
  • Father and Mother subject IDs are now shown in Analysis Overview page when pedigree information exists when analysis was run for reference.

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  • New Position detail in the variant panel provides copyable position text and links to genome browsers (IGV and UCSC) to streamline review of raw read pileups or other local information.

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Content versions:

Ingenuity Knowledge Base (Zosma_131203.000), COSMIC (v67), dbSNP (Build 138 (08/09/2013)), 1000 Genome Frequency (v3), TargetScan (v6.2), EVS (ESP6500 0.0.21), JASPAR (10/12/2009), PhyloP hg18 (11/2009), PhyloP hg19 (01/2009), Vista Enhancer hg18 (10/27/2007), Vista Enhancer hg19 (12/26/2010), CGI Genomes (11/2011), SIFT (01/2013), BSIFT (01/2013), TCGA (09/05/2013), PolyPhen-2 (HumVar Training set 2011_12), Clinvar (10/01/2013)


 

Release 2.3.20131107

New Features/Fixes:

  • Import in-house (INFO) annotations from VCF files as custom annotations during Analysis creation.

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  • Set your preferred default Variant table annotations to be shown for all your analyses.

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  • Create analysis sample search now returns samples with matching clinical feature annotations.
  • Confidence Filter Passed upstream pipeline filter option is enabled for CGI var files.
  • Mendelian inheritance genetics filter now also retains heterozygous variants in parents that are not transmitted to any child.

Content Versions:

Ingenuity Knowledge Base (Zildun_131104.000), COSMIC (v66), dbSNP (Build 138 (08/09/2013)), 1000 Genome Frequency (v3), TargetScan (v6.2), EVS (ESP6500 0.0.21), JASPAR (10/12/2009), PhyloP hg18 (11/2009), PhyloP hg19 (01/2009), Vista Enhancer hg18 (10/27/2007), Vista Enhancer hg19 (12/26/2010), CGI Genomes (11/2011), SIFT (01/2013), BSIFT (01/2013), TCGA (09/05/2013), PolyPhen-2 (HumVar Training set 2011_12), ClinVar (08/01/2013)


Release 2.2.20131017

New Features/Fixes:

  • Pathways page now provides list of drugs ordered by their ability to counteract the impact of mutations on the pathway, with links to supporting literature evidence and drug view that provides summary of the compounds’ pharmacology, clinical trials, and targets.

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  • SKAT-O algorithm (which automatically optimizes between burden test and association test) is now used by the Statistical Association filter (Case or Control option), to identify genes or pathways with an excess burden of rare variants (the p-values and optimal weights are shown in the corresponding Genes or Pathways pages).
  • Gene panel samples may now be purchased directly within the application.
  • Performance enhancements for large analyses.

Release 2.2.20130919

New Features/Fixes:

  • Variants that fall within ENCODE transcription factor binding sites can now be selected in the Predicted Deleterious filter.

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  • A new “ENCODE TFBS” Regulatory Site indicates regions observed to be bound by a transcription factor (specified in the Regulators column and the Variant details view).

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  • The Variant table search box now does exact gene symbol matches when quoted and supports dbSNP rs number search.
  • COSMIC identifiers can now be added to the Variant table view via Edit Columns.
  • The Fused to annotation now indications chromosomal breakpoint location of fusion partner.

Content Versions:

Ingenuity Knowledge Base (Yildun__130911.001), COSMIC (v65), dbSNP (Build 138 (08/09/2013)), 1000 Genome Frequency (v3), TargetScan (v6.2), EVS (ESP6500 0.0.21), JASPAR (10/12/2009), PhyloP hg18 (11/2009), PhyloP hg19 (01/2009), Vista Enhancer hg18 (10/27/2007), Vista Enhancer hg19 (12/26/2010), CGI Genomes (11/2011), SIFT (01/2013), BSIFT (01/2013), TCGA (09/05/2013), PolyPhen-2 (HumVar Training set 2011_12), Clinvar (08/01/2013)


Release 2.1.20130815

New Features/Fixes:

  • Confidence Filter passed upstream pipeline enabled for Complete Genomics samples.
  • New analyses are shown in ‘queued’ status until they start ‘running’.
  • VCF export documentation enhanced.
  • Genetic Analysis filter now defaults to paired for tumor: normal pair with same subject ID.
  • Samples that were paid activated whose term has expired now have ‘expired’ status.
  • Sample expiration dates added to My Samples details panel and export.
  • Notification added for renewal-eligible activated samples nearing expiration.

Release 2.1.20130621

New Features/Fixes:

  • Usability improvements including legends for pathway diagrams.

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Content Versions:

Ingenuity Knowledge Base (Xiphias _130613.000), COSMIC (v64), dbSNP (Build 137), 1000 Genome Frequency (v3), TargetScan (v6.2), EVS (ESP6500 0.0.19), JASPAR (10/12/2009), PhyloP hg18 (11/2009), PhyloP hg19 (01/2009), Vista Enhancer hg18 (10/27/2007), Vista Enhancer hg19 (12/26/2010), CGI Genomes (11/2011), SIFT (01/2013), BSIFT (01/2013), TCGA (5/14/2012), PolyPhen-2 (HumVar Training set 2011_12)


Release 2.0.20130604

New Features/Fixes:

  • Confidence Filter with Usual Suspects options for both most exonically variable genes and/or 100 base windows.

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  • High-volume upload using DataStream uploader using the link in the upload sample window.

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  • Simplification of the sample activation method.

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Release 2.0.20130517

New Features/Fixes:

  • Each user can now create multiple analyses at the same time, eliminating the need to wait to set up additional analyses.

Release 2.0.20130404

New Features/Fixes:

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Release 2.0.20130402

New Features/Fixes:

  • Easily re-use settings from another analysis to use the same filter cascade.
  • Include any custom annotations such as BED file(s) uploaded in the initial analysis or inheritance pattern selection.
  • Tentatively assign same case and control samples when creating a new analysis.

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  • The Legend now show the Confidence of a sample in lieu of the Call Quality.  For example in variant being present in each sample based on preceding Confidence Filter is now shown by dark (confident) versus light (not) color shading of Case and Control genotype icons

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  • Case (and Control) sample counts (and percentages) with variant now only include samples with Confident variant call in the Genes, Pathways, etc. summary tables.
  • The region into introns to consider for potential splice site mutations can now be increased from the canonical junctions (+/-2 nucleotides adjacent to exons) in the Predicted Deleterious filter. When enabled, intronic variants now are only counted as being in the gene by subsequent filters if they occur within this region to avoid counting overlapping genes.

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  • Now the HGVS Transcript Variant and Protein Variant columns include the coding and protein form qualifiers (c. and p. prefixes, respectively) to make the form explicit.

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  • A What’s New link will appears if there’s been a new product release since your last login. The Release Notes are also available from the online Help
  • The analysis Summary tab per-sample vertical stacked bar charts by value are now scaled by # variants (max across all samples) rather than % total variants within each sample. This better calls out visually if certain samples are skewed with many more variants than expected overall or for a particular value.

Release 2.0.20130314

New Features/Fixes:

  • Missense variants (majority of variants in a genome) can be selected for separately  from other types of (typically more deleterious) variants in Predicted Deleterious filter
  • PolyPhen-2 is now available to exclude variants it predicts are not functionally benign

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  • The gene details panel list for the Genes, Groups/Complexes, Pathways, Processes, and Diseases summary pages summarizes number of samples with variants in the gene for cases and controls as well as the inferred impact of the variants on the gene activities (loss, normal/carrier status, or gain of function).

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  • The click on a gene in the gene details panel jumps to Variants table with the gene in the search box to quickly see the corresponding variants
  • Summary tab now enables per-sample bar chart view of the values to quickly identify any outliers

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  • Exome server project data is distinguished between zero (no exomes with variant gets 0%) and no data, including in Common Variants filter.
  • Cytoband in Variant Details panel  is hyperlinked now to UCSC genome browser which enables quick access to multiple sequence alignments and chromosome and position details.

Release 2.0.20130228

New Features/Fixes:

  • Enabled any user to share a preview (or inactive analyses) with anyone (except him/herself)
  • Enabled VCF export of variant (single and multi-sample)
  • Now display ratio of transition vs. transversion frequencies in sample details view and in analysis overview for sample quality metrics
  • Tooltip added to compound-het
  • Canonical pathway view: display pathway summary and legend  ( Click on “I” icon to display)
  • Added quality-awareness for “mendelian/transient/de novo” filter in GA – a variant that fails to meet Confidence filter for a sample behaves as if it was not called in the sample
  • Multiple high-confidence junction files are supported for gene fusion

Release 2.0.20130214

New features / Fixes:

  • New Confidence filter enables multiple means of selecting variants based on quality considerations, including call confidence, PASS status from upstream variant calling pipeline, and read depth.
  • Call quality is migrated from Genetic Filter to a preceding Confidence Filter for existing analyses
  • Genetic Analysis and Statistical Association filters only count samples as having a variant which satisfy the Confidence filter selection criteria
  • Compound heterozygous specification is viewable and configurable for analyses
  • Variants that contribute to compound heterozygous status for a variant in any sample are shown in a table at the bottom of the Sample Details window
  • Variants that impact drug binding can now be selected with Pharmacogenetics filter
  • Pathway viewer enables Drug Targets to be highlighted
  • Symmetric gene and pathway burden test (C-Alpha)

Content Versions:

Ingenuity Knowledge Base (Wasat 130128.000), COSMIC (v62), dbSNP (Build 137), 1000 Genome Frequency (v3), TargetScan (v6.2), EVS (ESP6500 0.0.18), JASPAR (10/12/2009), PhyloP hg18 (11/2009), PhyloP hg19 (01/2009), Vista Enhancer hg18 (10/27/2007), Vista Enhancer hg19 (12/26/2010), CGI Genomes (11/2011), SIFT (01/2013), BSIFT (01/2013), TCGA (5/14/2012), PolyPhen-2 (HumVar Training set 2011_12Z


Release 1.3.20130124

New features / Fixes:

  • Sample search including over clinical features now can be done at Case/Control sample selection stage of analysis creation
  • Filter widgets updated to improve performance and provide vertical scroll bar for low resolution monitors
  • Genetic Analysis filter with gene-level exclude setting now excludes variants not kept in other group; default Genetic Analysis filter is now same-stringency gene-level keep and variant-level exclude

Release Notes Coming Soon