motifbreakR

Documentation

See motifbreakR vignette for an introduction to motifbreakR

See help("motifbreakR") for detailed help with running motifbreakR.

See help("plotMB") for detailed help with visualization.

Abstract

Functional annotation represents a key step toward the understanding and interpretation of germline and somatic variation as revealed by genome wide association studies (GWAS) and The Cancer Genome Atlas (TCGA), respectively. GWAS have revealed numerous genetic risk variants residing in non-coding DNA associated with complex diseases. For sequences that lie within enhancers or promoters of transcription, it is straightforward to assess the effects of variants on likely transcription factor binding sites. We introduce motifbreakR, which allows the biologist to judge whether the sequence surrounding a polymorphism or mutation is a good match, and how much information is gained or lost in one allele of the polymorphism relative to another or mutation vs. wildtype. MotifbreakR is flexible, giving a choice of algorithms for interrogation of genomes with motifs from public sources that users can choose from; these are 1) a weighted-sum, 2) log-probabilities, and 3) relative entropy. MotifbreakR can predict effects for novel or previously described variants in public databases, making it suitable for tasks beyond the scope of its original design. Lastly, it can be used to interrogate any genome curated within Bioconductor.

Install

Prepairing to install

You will need ghostscript: the full path to the executable can be set by the environment variable R_GSCMD. If this is unset a GhostScript executable will be searched by name on your path. For example on a Unix, Linux, or Mac environment gs will be used for searching, and on a Windows environment the setting of the environment variable GSC is used, otherwise commands gswi64c.exe and then gswin32c.exe are tried.

For example on Windows, assume that the gswin32c.exe is installed at C:\Program Files\gs\gs9.06\bin, open R then try: {r} Sys.setenv(R_GSCMD="\"C:\\Program Files\\gs\\gs9.06\\bin\\gswin32c.exe\"")

In Linux try your package manager to search for ghostscript. In Mac Homebrew serves as a great package manager. Windows can find it here

Additionally, one of the packages that we depend on depends upon MotIV in Bioconductor which in turn depends upon the GNU Scientific Library. Please see the MotIV Vignette, appendix: GSL Installation If you are having issues with installation.

If you'd like to make the vignette yourself (and have it appear identically to the one listed above), you also need pandoc which converts R markdown into any of numerous formats including .html, .pdf, and microsoft word style .doc files.

Getting prerequisite packages from Bioconductor

{r} if (!requireNamespace("BiocManager", quietly=TRUE)) install.packages("BiocManager") BiocManager::install(c("BiocParallel", "motifStack", "BSgenome", "BiocGenerics", "Biostrings", "GenomeInfoDb", "GenomicRanges", "Gviz", "S4Vectors", "rtracklayer", "IRanges", "MotifDb", "BSgenome.Hsapiens.UCSC.hg19", "SNPlocs.Hsapiens.dbSNP.20120608", "SNPlocs.Hsapiens.dbSNP155.GRCh37", "VariantAnnotation", "matrixStats", "BiocStyle")) install.packages(c("TFMPvalue", "knitr", "rmarkdown"))

Install motifbreakR from github

{r} install.packages("devtools") devtools::install_github("Simon-Coetzee/motifBreakR")