HerpesDRG is an open database of herpesvirus mutations and their impact on antiviral sensitivity.
This herpesdrg R package enables geneticists to make use of this database and annotate any present resistance mutations in herpesvirus sequencing data. Currently this includes HSV1, HSV2, HCMV, VZV, HHVb6.
Accepted variant file formats are VCF >= ver4.0 or Varscan2 tab, which must be assembled against the NCBI reference strain. Accepted sequence inputs are FASTA (whole genome, or genetic fragments), which are internally aligned to the reference.
For further information, or if you use HerpesDRG as part of your research, please cite the HerpesDRG article
The HerpesDRG database consists of over 1700 manually curated entries extracted from primary literature and detail the relationship between a
- Virus
- Gene
- Mutation
- Drug susceptibility fold change from sensitive strain or “Resistant” / “Polymorphism” as in publication
- The method for Resistance Phenotyping and strain generation
- Publication reference
A user-friendly Shiny Applications has been bundled with this package. The same application is available over the internet here http://cmv-resistance.ucl.ac.uk/herpesdrg/ where the terms of use are contained.
You can install the current version from GitHub with:
# install.packages("devtools")
devtools::install_github("ojcharles/herpesdrg")Dependencies for FASTA file handling are MAFFT and SNP-Sites available preferably via conda. snp-sites >= 2.3 has been tested.
conda config --add channels bioconda
conda install snp-sites
conda install mafftlibrary("herpesdrg")
## call resistant variants
my_sample = system.file("testdata", "HCMV_A10.vcf", package = "herpesdrg")
data = call_resistance(infile = my_sample, all_mutations = F, virus = "HCMV") # options are HSV1 HSV2 HCMV and VZV
data[ , c("change", "freq", "Ganciclovir", "Cidofovir", "Foscarnet", "Letermovir", "Maribavir", "ref_link")]
#> change freq Ganciclovir Cidofovir Foscarnet Letermovir Maribavir
#> 1 UL54_D588N 5.2% 2 1.3 2.8 NA
#> 2 UL54_D588N 5.2% 3.8 2.7 9 NA
#> 3 UL97_C592G 10.77% 3 NA
#> 4 UL97_C592G 10.77% 3 NA
#> 5 UL97_C592G 10.77% 3 NA
#> 6 UL97_H411Y 1.69% 0.5 12
#> 7 UL97_H411Y 1.69% 18
#> 8 UL97_T409M 37.13% 90
#> 9 UL97_T409M 37.13% 0.9 81
#> ref_link
#> 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059355/
#> 2 https://www.sciencedirect.com/science/article/pii/S1386653201001603?via%3Dihub
#> 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876423/
#> 4 https://aac.asm.org/content/55/1/382
#> 5 https://www.sciencedirect.com/science/article/pii/S0166354219304115?via%3Dihub
#> 6 https://jvi.asm.org/content/82/1/246.short
#> 7 https://www.sciencedirect.com/science/article/pii/S0166354219304115?via%3Dihub
#> 8 https://www.sciencedirect.com/science/article/pii/S0166354219304115?via%3Dihub
#> 9 https://academic.oup.com/jid/article/196/1/91/844651
## call all variants
mutations_all = call_resistance(infile = my_sample, all_mutations = T, virus = "HCMV")
#to view all mutations in resistance genes we can filter
mutations_res = mutations_all[mutations_all$GENEID %in% c("UL54", "UL97", "UL27", "UL51", "UL56", "UL89"),]
head(mutations_res[,c(1,8,21,32:40)],)
#> change freq CONSEQUENCE Ganciclovir Aciclovir Cidofovir
#> 996 UL51_T47M 99.88% nonsynonymous <NA> <NA> <NA>
#> 997 UL51_Y112Y 100% synonymous <NA> <NA> <NA>
#> 999 UL54_709 1.3% not translated <NA> <NA> <NA>
#> 1000 UL54_883 21.15% not translated <NA> <NA> <NA>
#> 1001 UL54_885 91.02% not translated <NA> <NA> <NA>
#> 1002 UL54_A1108T 99.05% nonsynonymous <NA> <NA> <NA>
#> Foscarnet Brincidofovir Letermovir Brivudine Penciclovir Tomeglovir
#> 996 <NA> NA <NA> <NA> <NA> NA
#> 997 <NA> NA <NA> <NA> <NA> NA
#> 999 <NA> NA <NA> <NA> <NA> NA
#> 1000 <NA> NA <NA> <NA> <NA> NA
#> 1001 <NA> NA <NA> <NA> <NA> NA
#> 1002 <NA> NA <NA> <NA> <NA> NA
## call nonsynonymous variants
# are there any non-synonymous (DNA variants that result in a change of amino acid) variants in resistance genes
mutations_res_nonsyn = mutations_all[mutations_all$GENEID == "UL54" & mutations_all$CONSEQUENCE == "nonsynonymous",]
# here the 6 mutations are nonsynonymous, with no identified resistance effect.
head(mutations_res_nonsyn[,c("change", "freq", "CONSEQUENCE", "Ganciclovir", "Foscarnet", "ref_title")],)
#> change freq CONSEQUENCE Ganciclovir Foscarnet
#> 1002 UL54_A1108T 99.05% nonsynonymous <NA> <NA>
#> 1004 UL54_A692V 100% nonsynonymous <NA> <NA>
#> 1007 UL54_D588N 5.2% nonsynonymous 2 2.8
#> 1008 UL54_D588N 5.2% nonsynonymous 3.8 9
#> 1018 UL54_L897S 99.82% nonsynonymous <NA> <NA>
#> 1019 UL54_N1116K 1.16% nonsynonymous <NA> <NA>
#> ref_title
#> 1002 <NA>
#> 1004 <NA>
#> 1007 Phenotypic Diversity of Cytomegalovirus DNA Polymerase Gene Variants Observed after Antiviral Therapy
#> 1008 Variations in the cytomegalovirus DNA polymerase and phosphotransferase genes in relation to foscarnet and ganciclovir sensitivity
#> 1018 <NA>
#> 1019 <NA># herpesdrg accepts sequence fragments or whole-genomes, one fasta sequence at a time.
# load example data
my_sequence = system.file("testdata", "HSV1_F716L.fasta", package = "herpesdrg")
dat = call_resistance(infile = my_sequence, all_mutations = F,virus = "HSV1")
#> [1] "fasta found"
head(dat[,c("change", "freq", "REFCODON", "VARCODON", "virus","Aciclovir", "Cidofovir", "Penciclovir", "ref_doi")])
#> change freq REFCODON VARCODON virus Aciclovir Cidofovir Penciclovir
#> 1 UL30_F716L 100% TTC CTC HSV1 6 0.1 2.2
#> ref_doi
#> 1 doi: 10.1128/AAC.49.2.606-611.2005## view the full database
db = herpesdrg_data()
head(db$aa_change)
#> [1] "D301N" "C304S" "N408D" "N408K" "N408S" "N410K"
## run the shiny application
# ShinyHerpes()If you encounter a clear bug, please file an issue with a minimal reproducible example on the GitHub Issues page. For questions and other discussions feel free to contact. Oscar Charles - maintainer