In ucl-pathgenomics/cmvdrg: Human CMV Drug Resistance Genotyping

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cmvdrg

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. ```{bash, eval=FALSE} conda config --add channels bioconda conda install snp-sites conda install mafft

## Usage

```r
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")]


#----- 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)])

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)


#----- 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 documentation built on Dec. 8, 2020, 2:36 a.m.