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@MichaelStromberg MichaelStromberg released this 23 Feb 06:19
· 301 commits to main since this release
v3.2.6
5a90d5d

This is the latest release in our Nirvana 3.2.x branch series used by the TruSight Oncology team at Illumina. This release uses the latest and greatest transcripts and genes directly from RefSeq.

Running Nirvana

Nirvana 3.2.6 has some difference compared with Nirvana 3.2.5:

  • the cache data now comes directly from RefSeq rather than from VEP. As such there are slight differences. For example, RefSeq uses official Sequence Ontology terms for the transcript biotypes rather than the related Ensembl terminology.
  • Phantom variant recomposition has been disabled for the time being
  • SIFT and PolyPhen are currently not available in the normal cache, but they are available for the transcripts in our CDx cache
  • the Nirvana command-line now asks for a cache directory rather than a cache path prefix

A typical Nirvana 3.2.6 command-line might look like this:

dotnet bin/Nirvana.dll -i NA12878.vcf.gz -c Data/Cache/GRCh37 -r Data/References/Homo_sapiens.GRCh37.Nirvana.dat --sd Data/SupplementaryAnnotation/GRCh37 -o NA12878

Installation

Download the files

mkdir Nirvana-3.2.6
cd Nirvana-3.2.6
wget https://nirvana-prerelease.s3.us-west-2.amazonaws.com/Reference-GRCh37.zip
wget https://github.com/Illumina/Nirvana/releases/download/v3.2.6/Nirvana-3.2.6-dotnet-6.0.zip
wget https://nirvana-prerelease.s3.us-west-2.amazonaws.com/Cache-GRCh37-RefSeq.zip
wget https://nirvana-prerelease.s3.us-west-2.amazonaws.com/Cache-GRCh37-CDx.zip
wget https://nirvana-prerelease.s3.us-west-2.amazonaws.com/Cache-HGNC-GeneSymbols.zip
wget https://nirvana-prerelease.s3.us-west-2.amazonaws.com/Cache-TSO500-GeneSymbols.zip
wget https://nirvana-prerelease.s3.us-west-2.amazonaws.com/Sift-CDx-VEP91.zip
wget https://nirvana-prerelease.s3.us-west-2.amazonaws.com/PolyPhen-CDx-VEP91.zip

Unpack Nirvana

mkdir -p bin Data/Cache/GRCh37 Data/References Data/SupplementaryAnnotation/GRCh37
cd bin
unzip ../Nirvana-3.2.6-dotnet-6.0.zip

Unpack the data files

cd ../Data/Cache/GRCh37
unzip ../../../Cache-GRCh37-RefSeq.zip
unzip ../../../Cache-GRCh37-CDx.zip
unzip ../../../Cache-TSO500-GeneSymbols.zip
cd ../../References
unzip ../../Reference-GRCh37.zip
cd ../SupplementaryAnnotation/GRCh37
unzip ../../../Sift-CDx-VEP91.zip
unzip ../../../PolyPhen-CDx-VEP91.zip
cd ../../..

In the example above, we're unpacking the gene symbols (Cache-TSO500-GeneSymbols.zip) that were used in Nirvana 3.2.5. If you want the latest gene symbols from HGNC as of 2022-02-21, unpack the Cache-HGNC-GeneSymbols.zip file instead.

Checking the installation

dotnet bin/Nirvana.dll

You should see the following:

---------------------------------------------------------------------------
Nirvana                                             (c) 2022 Illumina, Inc.
Stromberg, Roy, Siddiqui, Platzer, et al.                             3.2.6
---------------------------------------------------------------------------

USAGE: dotnet Nirvana.dll -i <vcf path> -c <cache dir> --sd <sa dir> -r <ref path> -o <base output filename>
Annotates a set of variants

OPTIONS:
      --cache, -c <dir>      input cache dir
      --in, -i <path>        input VCF path
      --gvcf                 enables genome vcf output
      --vcf                  enables vcf output
      --out, -o <file path>  output file path
      --ref, -r <path>       input compressed reference sequence path
      --sd <directory>       input supplementary annotation directory
      --force-mt             forces to annotate mitochondrial variants
      --help, -h             displays the help menu
      --version, -v          displays the version

Cache version: 1, Supplementary annotation version: 50, Reference version: 7

If this doesn't work, you might need to install either the .NET 6.0 runtime or the .NET 6.0 SDK. However, if you're only running Nirvana, you only need the runtime.

Features

Issue key Summary
NIR-920 Add support for MT transcripts
NIR-879 Add gene symbol override to Nirvana
NIR-876 Add support for discovering amino acid edits (non-canonical start codons, etc.)
NIR-872 Add support for RefSeq regulatory regions
NIR-798 Add support for multiple caches belonging to the same genome assembly
NIR-438 Create RefSeq Cache v28 files

Bugs fixed

Issue key Summary
NIR-1036 Resolve consequence issues that were identified in VEP 105 comparison
NIR-703 Nirvana incorrectly handles deletions across the terminal codon in HGVS p.
NIR-56 CDS position goes beyond the CDS sequence length (NM_001300952.1)

Unresolved bugs

Issue key Summary Fix Version
NIR-919 Nirvana does not handle protein sequences that are partially aligned to the genome
NIR-918 Nirvana does not handle ribosomal frameshifts properly during translation
NIR-721 Nirvana does not properly preload <NON_REF> variants 3.9.0
NIR-714 Nirvana should trim and LS variants during TopMed lift-over using dbSNP IDs 3.9.0
NIR-719 Nirvana does not remove missing values in 1KG SV IDs 3.8.0
NIR-722 Nirvana does not throw error when annotating unsorted VCF file 3.6.0
NIR-718 Nirvana reports zero allele frequencies for 1KG SV supplementary annotations 3.6.0
NIR-717 Nirvana does not annotate properly when variants fall into transcript gaps 3.5.0
NIR-713 Nirvana cannot handle OMIM phenotype 617956 (β-glucopyranoside tasting) 3.5.0
NIR-720 Nirvana creates empty custom annotations 3.3.0
NIR-716 Nirvana should assign copy_number_loss to <DEL> with SVTYPE=CNV 3.3.0
NIR-715 Nirvana provides extra PhyloP scores for some genomic positions 3.3.0
NIR-712 Nirvana is missing dbSNP annotations for mitochondrial variants 3.3.0
NIR-701 Nirvana should simplify HGVS p. notation for deletions that disrupt the initiation codon
NIR-86 Nirvana should use the transcript sequence for HGVS c. instead of reference
Assets 3
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