cmvdrg

GitHub repo
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overview

cmvdrg is a R package to enable antiviral drug resistance genotyping, with Human Cytomegalovirus sequencing data. Accepted inputs are FASTA (whole genomes & fragments) which will be mapped to RefSeq NC_006273.2. NGS variant data assembled to NC_006273.2 is accepted in VCF >= ver4.0 & Varscan2 tab formats.

Database

Contains the relationships between:

Mutation
Drug susceptibility, values are EC50 fold changes to susceptible strains. “Susceptible” or “Resistant” are present if data is anecdotal.
The method for Resistance Phenotyping, including where possible strain information used in marker transfer. i.e. AD169, TOWNE.
Publication reference, DOI, web address & review paper reference if used.
Where a co-mutation susceptibility profile is available for a known drug, this is included.
Administrative information, last update to row & whether it is used in calculations or not. i.e. A “Active”" is included, where there is ambiguity the status field is “U” Unused, or “R” to Review

Web service

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/cmvdrg/ where the terms of use are contained.

Installation

You can install the current version from GitHub with:

# install.packages("devtools")
devtools::install_github("ucl-pathgenomics/cmvdrg")

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 mafft

Usage

library("cmvdrg")

#----- call resistant variants
my_sample = system.file("testdata", "A10.vcf", package = "cmvdrg")

data = call_resistance(infile = my_sample, all_mutations = F,inc_anecdotal = F)

data[ , c("change", "freq", "Ganciclovir", "Maribavir", "Foscarnet", "ref_doi")]
#>       change   freq Ganciclovir Maribavir Foscarnet
#> 1 UL54_D588N   5.2%           2                 2.8
#> 2 UL54_D588N   5.2%         3.8                   9
#> 3 UL97_C592G 10.77%           3                    
#> 4 UL97_C592G 10.77%           3                    
#> 5 UL97_C592G 10.77%           3                    
#> 6 UL97_H411Y  1.69%                    18          
#> 7 UL97_H411Y  1.69%         0.5        12          
#> 8 UL97_T409M 37.13%                    90          
#> 9 UL97_T409M 37.13%         0.9        81          
#>                                           ref_doi
#> 1                  doi: 10.1016/j.jcv.2011.01.004
#> 2   https://doi.org/10.1016/S1386-6532(01)00160-3
#> 3                            10.1128/AAC.00186-10
#> 4       https://dx.doi.org/10.1128%2FAAC.01259-10
#> 5 https://doi.org/10.1016/j.antiviral.2019.104616
#> 6 https://doi.org/10.1016/j.antiviral.2019.104616
#> 7                       DOI: 10.1128/JVI.01787-07
#> 8 https://doi.org/10.1016/j.antiviral.2019.104616
#> 9                  https://doi.org/10.1086/518514

#----- call all variants
mutations_all = call_resistance(infile = my_sample, all_mutations = T)

#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"),]

# are there any non-synonymous (DNA variants that result in a change of amino acid) variants in resistance genes
mutations_res_nonsyn = mutations_res[mutations_res$CONSEQUENCE == "nonsynonymous",]

# here the top 3 mutations are nonsynonymous, with no identified resistance effect.
head(mutations_res_nonsyn[,c(1,8,21,32:40)])
#>           change   freq   CONSEQUENCE Ganciclovir Cidofovir Foscarnet
#> 996    UL51_T47M 99.88% nonsynonymous        <NA>      <NA>      <NA>
#> 1002 UL54_A1108T 99.05% nonsynonymous        <NA>      <NA>      <NA>
#> 1004  UL54_A692V   100% nonsynonymous        <NA>      <NA>      <NA>
#> 1007  UL54_D588N   5.2% nonsynonymous           2       1.3       2.8
#> 1008  UL54_D588N   5.2% nonsynonymous         3.8       2.7         9
#> 1018  UL54_L897S 99.82% nonsynonymous        <NA>      <NA>      <NA>
#>      Brincidofovir Letermovir Tomeglovir GW275175 Maribavir Cyclopropavir
#> 996             NA       <NA>         NA       NA      <NA>            NA
#> 1002            NA       <NA>         NA       NA      <NA>            NA
#> 1004            NA       <NA>         NA       NA      <NA>            NA
#> 1007            NA                    NA       NA                      NA
#> 1008            NA                    NA       NA                      NA
#> 1018            NA       <NA>         NA       NA      <NA>            NA

other functionality

#----- visualise variants
plot_lollipop(data, "UL97")


#----- Generate a clinical overview of strain sensetivity
#clin_table = make_clin_table(data)

#-----view the full database
db = cmvdrg_data()
head(db$aa_change)
#> [1] "D301N" "C304S" "N408D" "N408K" "N408S" "N410K"

#----- run the shiny application
# runShinyCMV()

Getting help

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

ucl-pathgenomics / cmvdrg

readme