Process paired tumor-normal VCF variants annotated with SnpEff for neoantigen prediction using garnish_affinity.

garnish_variants(vcfs, tumor_sample_name = "TUMOR")

Arguments

vcfs

Paths to one or more VFC files to import. See details below.

tumor_sample_name

Character, name of column in vcf of tumor sample, used to determine mutant allelic fraction of neoantigens.

Value

A data table with one unique SnpEff variant annotation per row, including:

  • sample_id: sample identifier constructed from input .vcf file names

  • se: SnpEff annotation

  • effect_type: SnpEff effect type

  • ensembl_transcript_id: transcript effected

  • ensembl_gene_id: gene effected

  • protein_change: protein change in HGVS format

  • cDNA_change: cDNA change in HGVS format

  • protein_coding: is the variant protein coding?

if CF or AF fields in provided in input VCFs, either:

  • cellular_fraction: cell fraction taken from input, such as from clonality estimates from PureCN

  • allelic_fraction: allelic fraction taken from input

Details

vcfs must be annotated with SnpEff. vcfs can optionally contain an AF or CF INFO field, in which case cellular fraction or allelic fraction is considered when ranking neoantigens. See example vcf. Single samples are required. Multi-sample vcfs are not supported.

Recommended workflow:

  1. Call variants using MuTect2 and Strelka2, intersecting variants.

  2. Variant filtering according to experimental specifications.

  3. Classification by somatic status and clonality using PureCN.

  4. Annotate variants using SnpEff (required).

References

Krøigård AB, Thomassen M, Lænkholm A-V, Kruse TA, Larsen MJ. 2016. Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data. PLoS ONE. 11(3):e0151664

Cingolani P, Platts A, Wang LL, Coon M, Nguyen T, et al. 2012. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin). 6(2):80–92

Riester M, Singh AP, Brannon AR, Yu K, Campbell CD, et al. 2016. PureCN: copy number calling and SNV classification using targeted short read sequencing. Source Code Biol Med. 11(1):13

Callari M, Sammut SJ, De Mattos-Arruda L, Bruna A, Rueda OM, Chin SF, and Caldas C. 2017. Intersect-then-combine approach: improving the performance of somatic variant calling in whole exome sequencing data using multiple aligners and callers. Genome Medicine. 9:35.

See also

Examples

if (FALSE) { library(magrittr) library(data.table) library(antigen.garnish) # load an example VCF dir <- system.file(package = "antigen.garnish") %>% file.path(., "extdata/testdata") dt <- "antigen.garnish_example.vcf" %>% file.path(dir, .) %>% # extract variants garnish_variants %T>% str }