Variant Analysis Release Notes

Release  3.1.20141014

New Features: 

  • Pre-Filtering – To optimize the loading of large cohort studies (greater than: 200 genomes or 2000 exomes) Variant Analysis now features a pre-filter step as part of the Analysis Setup Wizard.  Now users can apply some of  the filters available in the Filter Cascade during the pre-analysis step to optimize system resources by focusing on exonic regions, high quality variants or likely causal variants typically absent in a “normal” population.  Users who are interested in disabling this feature may do so by contacting Ingenuity Customer Support.

VR Rel 101414 1_Pre-filter

 

  • Filtering on Copy Number Variants – Variant Analysis now accepts Copy Number Variation (CNV) information specified as a range of bases along with it’s copy number in the VCFS files.   Ingenuity Variant Analysis will refer the VCF’s copy number for the variants that occur within the CNV range. This CNV value will supersede the Variant Analysis-inferred CNV value.   A max CNV value of 9 is supported with values above 9 cited as 9.   Variants that occur in overlapping CNV region with different CNV values will be assigned the higher CNV value. 

This update to Variant Analysis currently does not support the following CNV information if provided in the VCF file:

  • DUP:TANDEM Tandem duplication
  • DEL:ME Deletion of mobile element relative to the reference
  • INS:ME Insertion of a mobile element relative to the reference

VR Rel 101414 2_CNV

 

  • Splice Site Prediction – New for this release is the ability to predict the effects of single nucleotide variations (SNV) on splice sites within the Predicted Deleterious Filter window.   Based on MaxEntScan the Variant Analysis algorithm will predict the following mutation event outcomes:
    • Exon truncation
    • Exon extension
    • Exon skipping 

 

VR Rel 101414 3_Splice Site

 

This feature is available within the Predicted Deleterious Filter.

VR Rel 101414 4_Predicted D Filter

 

Further explanation of the prediction is shown in the Details page.

VR Rel 101414 5_Predicted details 

 

  • HGMD Content Support – Now HGMD content will be displayed as annotations within Variant Analysis.   While hyperlinks to the HGMD Pro portal will remain, the HGMD annotations are now included alongside all other available annotations for the variant.   Please note, HGMD content will only be displayed if available for the variant.

VR Rel 101414 6_HGMD Annotated

 

  • HGMD Variant Filter – A new feature available within the Predicted Deleterious Filter window that limits the filtered selection to HGMD annotated variants.

VR Rel 101414 6_HGMD content


 

Release 3.1.20140919

  • Quantitative Traits filter – To correlate variants with degree of severity of a phenotype, Ingenuity Variant Analysis now features a tool to find variants that may contribute to severity of an observed trait. This feature is available within the Statistical Association filter and requires the user to upload the trait(s) of interest using the upload annotations features.  Additionally all samples to be filtered using this feature must have a non-null value for its trait of interest. Acceptable values for a trait’s degree of severity include Boolean or numeric. The feature currently does not accept traits with more than 2 alphanumeric values for trait severity (ex. Acceptable: “yes’, “no”; Non-acceptable: “yes, “no”, “maybe”).

Qualitative Trait in Ingenuity Variant Analysis.

  • Option to remove existing annotations – Allow removing of existing annotations: previously users cannot remove existing annotations. Now users can do so by using a file with the matched annotation column but with blank value for the sample.
  • EGFR Exon 19 deletion gain of function – Within exon 19 of EGFR gene, any variant causing in-frame deletion or insertion through nucleotide deletion, insertion or substitution will have a Gain of Function call for Inferred Activity.
  • Mini Findings – Fast, breaking scientific articles referencing the identified variant. These articles have yet to be deeply curated by our expert curation team are provided to the user as the latest most up-to-the-minute findings in the scientific literature with detailed curation to come soon.
  • Others:

Updated dbsnp version from 138 to 141

Updated EVS from 0.0.21 to 0.0.28

Content versions:
Ingenuity Knowledge Base (Baslag 140721.001), COSMIC (v68), dbSNP (Build 141 (05/21/2014)), 1000 Genome Frequency (v3), TargetScan (v6.2), EVS (ESP6500 0.0.28), 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 (02/11/2014)


 

Release 3.1.20140729

New Features/Fixes:

  • Segregation by family/kindred functionality - New for this release is the ability to segregate samples by their family relationship. This feature is available in the Genetic Analysis filter and requires an uploaded PED file to describe the familiar relationship between samples to be segregated. One may segregate families of samples by gene or by variant.

Family

  • Enhanced Field Filtering – To enhance search for samples, Ingenuity Variant Analysis now automates search for samples using a one-click feature by clicking on a sample’s attribute fields that are highlighted in gray. A simple click on one of these gray-highlighted fields quickly narrows your samples list to all samples that match that field’s value. Available gray-highlighted fields may be system created fields or fields uploaded via the annotations upload feature.

Screen Shot 2014-08-05 at 11.11.31 AM

  • Option to disable auto-recalculate for filter changes – A feature to greatly reduce time when changing multiple filter settings is the option to disable auto-recalculate. Users can now make multiple changes to the filter cascade without the system performing a recalculate step for each filter cascade change which may take several minutes. By unchecking the auto-recalculate, users can now make multiple changes to the filter cascade, and then with one click, apply all changes in one step thereby making iterative changes to the filter cascade faster.

Screen Shot 2014-08-05 at 11.25.09 AM

  • Update of the computed assessments and inferred sex algorithms.

Content Versions:

Ingenuity Knowledge Base (Baslag 140721.001), COSMIC (v68), dbSNP (Build 141 (05/21/2014)), 1000 Genome Frequency (v3), TargetScan (v6.2), EVS (ESP6500 0.0.28), 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 (02/11/2014)


Release 3.0.20140520

New Features/Fixes:

  • Variant Analysis now integrates HGMD content from Biobase. Learn More

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Release 3.0.20140417

New Features/Fixes:

  • Analysis with 200 or less whole genome samples  can optionally be pre-filtered to only include intronic regions +/- 20bp flanking . This will result in faster time to results and more efficient use of resources.

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  • Computed assessments are now based on latest draft ACMG 2014 guidelines, including frameshifts in genes implicated in diseases where loss of function is a known mechanism of action. This may cause some variants which previously had uncertain significance to now be (likely) pathogenic and pass through Predicted Deleterious filters.
  • HGVS nomenclature refinements.
  • Normalization of INDEL display across file format.
  • Improved sample(s) and analysis status with end date, color indicator and filtering.

Content Versions:
Ingenuity Knowledge Base (Arrakis 140408.002), COSMIC (v68), 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 (02/11/2014)


Release 2.4.20140307

New Features/Fixes:

  • Implementation of dynamic assessment using ACMG Draft clinical assessments along with a details panel indicating the list of supporting evidence for (+) pathogenicity or against (-). For more details on how the assessment’s determination is made, please contact Ingenuity Product Support at support@ingenuity.com.

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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 2.4.20140207

New Features/Fixes:

  • Confidence filter permits filtering on sample-specific allele fraction.

Screen Shot 2014-02-07 at 8.40.53 AM

  • Enable export to QIAGEN’s Ingenuity Pathway Analysis for end-users with an IPA product license.

Screen Shot 2014-02-07 at 8.41.36 AM

  • HGVS nomenclature refinements- including 3’ shift of indels relative to transcript.
  • Analysis containing more than 200 whole genome sequencing (WGS) samples will automatically exclude functionally uncharacterized non-genic and deep intronic segments. This will result in faster time to results and more efficient use of resources. Users can still opt to analyze the entire genome for sample sizes greater than 200 by contacting Ingenuity Product Support.

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.

mito

  • 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.

ec

  • 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.

over

  • 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.

igv

 

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.

Screen Shot 2013-11-07 at 9.32.05 AM

 

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

Screen Shot 2013-11-07 at 9.33.24 AM

 

  • 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.

Screen Shot 2013-10-17 at 10.03.27 AM

  • 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.

Untitled

  • 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).

Screen Shot 2013-09-19 at 8.53.23 AM

  • 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.

Path2Phenotype-Legend

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.

Screen Shot 2013-06-04 at 7.13.19 PM

  • 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

2012 Releases Summary

  • Introduction of a Statistical Association Filter to select variants based on rare association, p-value or odds ratio.
  • Publish feature: pick a stable URL that links an article you’re submitting to a copy of your analyzed dataset that readers can use for free – the ultimate online supplement!
  • Enhanced Genetic Analysis filter enables restricting to variants that are transmitted or de novo when family relationship information is present.
  • Many contents enhancement including Polyphen-2, haploinsufficiency, pharmacogenetic and TCGA.