Variant Analysis Release Notes 2014

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

Screen Shot 2014-05-16 at 11.44.16 AM


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.

Screen Shot 2014-04-18 at 10.00.46 AM

  • 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.

Screen Shot 2014-03-06 at 7.54.10 AM

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.