---

Torrent Suite Software space on Ion Community

Analysis Report Guide TOC

Ion Reporter Software Features Related to Variant Calling

Both Ion Reporter Software (IR) and Torrent Suite Software (TSS) offer the Torrent Variant Caller and both provide a list of the variant positions called. This page describes additional features that are available in Ion Reporter Software.

In particular, the automated annotations, links to public databases, and near real-time filtering in the IR UI provide time savings for researchers.

Annotations

In addition to the listing of the variant calls and positions, IR also annotates your called variants with information from both publicly and private databases. Except where noted, t hese annotations are pre-built within IR. You can select which of these annotation sources to include in your analysis workflows.

The following annotation sources are packaged with IR:

• dbSNP The Single Nucleotide Polymorphism Database, a free public-domain archive for simple genetic polymorphisms, at the following site:

www.ncbi.nlm.nih.gov/projects/SNP

• COSMIC The Catalogue of Somatic Mutations in Cancer, which contains information about somatic mutations in cancer, with more than 100,000 somatic mutations from approximately 400,000 tumors. From their websites:

http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/about.html

http://www.sanger.ac.uk/resources/databases/cosmic.html

• OMIM From the website http://www.ncbi.nlm.nih.gov/omim:

"Online Mendelian Inheritance in Man. OMIM is a comprehensive, authoritative, and timely compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known Mendelian disorders and over 12,000 genes. OMIM focuses on the relationship between phenotype and genotype."

• GeneModel Ensembl or RefGene sources.

• GenePanel Genomic regions panels that you download from AmpliSeq.com or your own custom panels.

• SIFT scores A SIFT score predicts whether an amino acid substitution affects protein function.

• PolyPhen-2 scores The PolyPhen2 score predicts the possible impact of an amino acid substitution on the structure and function of a human protein.

• Grantham scores The Grantham score attempts to predict the distance between two amino acids, in an evolutionary sense.

• PhyloP PhyloP scores measure evolutionary conservation at individual alignment sites and report either slower evolution than expected or faster evolution than expected. For more information, visit this site and click the PhyloP link on the site's left navigation panel:

compgen.bscb.cornell.edu/phast/background.php

• Gene Ontology The Gene Ontology project aims to standardize the representation of gene and gene product attributes across species and databases by providing a controlled vocabulary of terms for describing gene product characteristics and gene product annotation data. The Gene Ontology Consortium is supported by a grant from the National Human Genome Research Institute (NHGRI). See the following sites for more information:

http://geneontology.org

http://amigo.geneontology.org

• Pfam From their website at http://pfam.sanger.ac.uk: "The Pfam database is a large collection of protein families, each represented by multiple sequence alignments and hidden Markov models".

• Ingenuity Variant Analysis Software This is not a pre-built annotation source. From IR, you export your IR variants to this site to take advantage of the insight and filtering that Variant Analysis offers. If you have a large number of new variants in an analysis, Variant Analysis Software can help you filter the large set down to the most interesting variants, based to pathways, literature citations, and other categories. You can then import your variant set back into IR.

• Local annotation sources These are specific to your IR organization and are not pre-built annotation sources. You can configure annotation sources for the following:
  • Maintain a list of significant variants seen in your research
  • Flag variants seen previously in your research or of particular interest to your organization
  • Import positions in ampliseq.com panels
  • Contain your custom free-form annotations for specific positions
  • Limit variant calls to your list of preferred transcripts
  • Filter out known false positives

Notes on IR annotations:

• The use of ONCOMINE annotations and the Ingenuity Variant Analysis Software site involve additional charges.
  
  
• IR typically adds more annotation sources with each new release.
• Annotation is a separate module in IR workflows, called after the variant caller module. IR also has a workflow that only does annotations. This workflow takes a VCF input file of variant calls and adds annotations to those variants.

Multiple-sample workflows

IR offers pre-built workflows for paired or trio related samples. During variant review, you can compare the incidence of variants in related samples. Variant calls in TSS are on one sample at a time.

IR also offers the pre-built Tumor/Normal workflow for a pair of input samples where one sample is a tumor sample and the other is a normal sample form the same individual. Tumor/Normal workflow provides more than a comparison of the presence of variants in each sample. For candidate variant positions seen in the tumor sample, the Tumor/Normal workflow also checks the background levels of those variants in the normal sample, providing an analysis of statistical significance of candidate variants in the tumor sample.

Additional variant types

IR workflows support additional variant types that TSS does not call. These include copy number variation and genetic disease variants such as compound heterozygous, trans-phase compound heterozygous, and male maternal X.

The IR Genetic Disease Screening workflow also contains a pedigree check, which finds mis-labeling of the samples or mis-identification of the parent samples.

Variant filters, links, and export

After your IR analysis completes, you can filter your called variants directly in the IR results review screen. For example, you can use pre-built filters to display only novel variants, or only variants that have an impact on the coded protein.

The filtering feature greatly reduces the effort required for you to review the results of large datasets. You can f ilter variants based on experimental or functional evidence. You can use IR's filters on the fly in the IR UI, or automate and reuse your filters.

Also on the IR results review screen, variant details include links to variant information in public databases such as dbSNP or COSMIC (when appropriate).

IR also offers a connection to the TaqMan Assays site during variant review of a completed analysis. This site returns the TaqMan SNP Genotyping Assay products related to your variants.

Output files

In IR you can download your variants in VCF format or as a text file.

Elasticity of the cloud

With larger datasets and in high-throughput labs, the use of IR takes some compute load off your Torrent Server and relieves strain on your Torrent Server compute resources.

Cost

Beginning with the IR 4.0 release, IR usage is connected to Thermo Fisher eCommerce. IR charges are based on the amount of storage used (with lower storage usage being free). Use of the Ingenuity Variant Analysis Software website involves a separate purchase.

IR space on the Ion Community

For more information about Ion Reporter Software, see the Ion Reporter Software space on the Ion Community.

---