Package TFutils. October 11, 2018

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1 Title TFutils Package to work with TF data. Version Depends R (>= 3.5.0) Package TFutils October 11, 2018 Imports methods, GenomicRanges, IRanges, S4Vectors, GSEABase, shiny, miniui, data.table, dplyr, magrittr, AnnotationDbi, Rsamtools, GenomeInfoDb, GenomicFiles, AnnotationFilter, GenomicFeatures, Gviz, utils, stats, Biobase Suggests knitr, DT, Homo.sapiens, GO.db, org.hs.eg.db, ensembldb, EnsDb.Hsapiens.v75, testthat, BiocParallel, BiocStyle, SummarizedExperiment, UpSetR, ggplot2 License Artistic-2.0 LazyLoad yes LazyData true VignetteBuilder knitr Roxygen biocviews Transcriptomics Roxygen list(markdown = TRUE) git_url git_branch RELEASE_3_7 git_last_commit 2f08b9b git_last_commit_date Date/Publication Author Vincent Carey [aut], Shweta Gopaulakrishnan [cre, aut] Maintainer Shweta Gopaulakrishnan <reshg@channing.harvard.edu> R topics documented: cisbptfcat fimo fimomap genemodeldf

2 2 cisbptfcat genemodforgviz grabtab gwascat_hg19_chr HGNCmap hocomoco.mono importfimo,tabixfile,granges-method importfimo_local_split metadata_tf named_tf show,tfcatalog-method TFCatalog TFCatalog-class tfhash TFtargs tftcoll tftcollmap URL_s3_tf Index 15 cisbptfcat cisbptfcat: data.frame with information on CISBP TFs for human cisbptfcat: data.frame with information on CISBP TFs for human cisbptfcat data.frame Extracted March select Homo_sapiens head(tfutils::cisbptfcat)

3 fimo16 3 fimo16 fimo16: GenomicFiles instance to AWS S3-resident FIMO bed for 16 TFs fimo16: GenomicFiles instance to AWS S3-resident FIMO bed for 16 TFs fimo16 GenomicFiles for a TabixFileList K. Glass ran FIMO TFutils::fimo16 fimomap fimomap: table with Mnnnn (motif PWM tags) and HGNC symbols for TFs fimomap: table with Mnnnn (motif PWM tags) and HGNC symbols for TFs fimomap data.frame Kimberly Glass (rekrg@channing.harvard.edu) head(tfutils::fimomap)

4 4 genemodforgviz genemodeldf use EnsDb to generate an exon-level model of genes identified by symbol use EnsDb to generate an exon-level model of genes identified by symbol genemodeldf(sym, resource, columnskept = c("gene_id", "tx_id"),...) sym resource columnskept... passed to exons() a character() vector of gene symbols should be or inherit from EnsDb, answering exons(), with AnnotationFilter::SymbolFilter as filter parameter character vector used as columns param in exons() data.frame instance with exons in rows There are many approaches available to acquiring gene models in Bioconductor; this one emphasizes the use of the exons method for Ensembl annotation. if (requirenamespace("ensdb.hsapiens.v75")) { orm = genemodeldf("ormdl3", EnsDb.Hsapiens.v75::EnsDb.Hsapiens.v75) dim(orm) } head(orm) genemodforgviz create a GeneRegionTrack instance for selected symbols create a GeneRegionTrack instance for selected symbols genemodforgviz(sym = "ORMDL3", id_elem = c("symbol", "tx_id"), resource = EnsDb.Hsapiens.v75::EnsDb.Hsapiens.v75,...)

5 grabtab 5 sym id_elem resource character vector of gene symbols, should be neighboring genes vector of names of columns generated by genemodeldf to be used to label transcripts should be or inherit from EnsDb, answering exons(), with AnnotationFilter::SymbolFilter as filter parameter... passed to genemodeldf instance of Gviz GeneRegionTrack This function helps to display the locations of TF binding sites in the context of complex gene models. A complication is that we have nice visualization of quantitative affinity predictions for TFs in the vignette, based on ggplot2, but it is not clear how to use that specific code to work with Gviz. if (requirenamespace("ensdb.hsapiens.v75") & requirenamespace("gviz")) { orm = genemodforgviz("ormdl3", resource= EnsDb.Hsapiens.v75::EnsDb.Hsapiens.v75) orm Gviz::plotTracks(orm, showid=true) # change id_elem for shorter id string } grabtab create table of TF targets and related metadata create table of TF targets and related metadata grabtab(tfstub = "STAT1", gscoll = TFutils::tftColl, orgdb = org.hs.eg.db::org.hs.eg.db, gwrngs = TFutils::gwascat_hg19_chr17) tfstub gscoll orgdb gwrngs character(1) gene-like symbol for TF; will be grepped in names(gscoll) a GSEABase GeneSetCollection an instance of OrgDb as defined in AnnotationDbi a GRanges representing EBI gwascat, must have DISEASE/TRAIT, MAPPED_GENE data.frame instance

6 6 HGNCmap This function will link together information on targets of a given TF to the GWAS catalog. gt = grabtab("vdr", gscoll=tfutils::tftcoll, orgdb=org.hs.eg.db::org.hs.eg.db, gwrngs=tfutils::gwascat_hg19_chr17) dim(gt) head(gt) gwascat_hg19_chr17 gwascat_hg19: GRanges of march EBI gwascat, limit to chr17 gwascat_hg19: GRanges of march EBI gwascat, limit to chr17 gwascat_hg19_chr17 GenomicRanges GRanges instance gwascat::makecurrentgwascat, with gwascat:::lo38to19 applied TFutils::gwascat_hg19_chr17[,1:5] HGNCmap simple accessor for HGNCmap component of TFCatalog simple accessor for HGNCmap component of TFCatalog HGNCmap(x) x instance of TFCatalog

7 hocomoco.mono 7 dataframe instance HGNCmap hocomoco.mono hocomoco.mono: data.frame with information on HOCOMOCO TFs for human hocomoco.mono: data.frame with information on HOCOMOCO TFs for human hocomoco.mono data.frame Extracted March head(tfutils::hocomoco.mono) importfimo,tabixfile,granges-method import a FIMO bed-like file import a FIMO bed-like file ## S4 method for signature 'TabixFile,GRanges' importfimo(src, parms,...) ## S4 method for signature 'character,missing' importfimo(src, parms,...)

8 8 importfimo_local_split src TabixFile instance parms a GRanges instance delimiting the import; multiple GRanges can be used... passed to GenomicRanges::GRanges instance of GRanges if (requirenamespace("rsamtools")) { tf = Rsamtools::TabixFile(system.file("M5946_1/chr1.bed.gz", package="tfutils")) importfimo(tf, GenomicRanges::GRanges("chr1", IRanges::IRanges(1e6,11e6))) } importfimo_local_split utility to read FIMO outputs from local resource(cluster), assuming bed text split by chromosome utility to read FIMO outputs from local resource(cluster), assuming bed text split by chromosome importfimo_local_split(tf, chr) tf chr character(1) file id character(1) chromosome name data.table instance requirenamespace("genomicranges") requirenamespace("iranges") importfimo_local_split("m5946_1", "chr1") dim(importfimo_local_split("m5946_1", "chr17"))

9 metadata_tf 9 metadata_tf metadata_tf: list with metadata (motif_if and hgnc_symbol) about all the CISBP FIMO scan TF bed files metadata_tf: list with metadata (motif_if and hgnc_symbol) about all the CISBP FIMO scan TF bed files metadata_tf list K. Glass ran FIMO TFutils::metadata_tf named_tf named_tf: named list with the names being the hgnc_symbol of the motif_id named_tf: named list with the names being the hgnc_symbol of the motif_id named_tf list K. Glass ran FIMO TFutils::named_tf named_tf[["vdr"]]

10 10 TFCatalog show,tfcatalog-method produce a concise report on TFCatalog instance produce a concise report on TFCatalog instance ## S4 method for signature 'TFCatalog' show(object) object instance of TFCatalog side effect TFCatalog Constructor for TFCatalog Constructor for TFCatalog TFCatalog(name, nativeids, HGNCmap, metadata) name nativeids HGNCmap metadata informative character(1) for collection character() vector of identifiers used by collection creators data.frame with column 1 nativeids, column 2 HGNC or hgnc.heur for MSigDb and any other columns of use a list of metadata elements instance of TFCatalog TFs_MSIG = TFCatalog(name="MsigDb.TFT",nativeIds=names(tftColl), HGNCmap=data.frame(tftCollMap,stringAsFactors=FALSE)) TFs_MSIG

11 TFCatalog-class 11 TFCatalog-class define a structure to hold information about TFs from diverse reference sources Slots define a structure to hold information about TFs from diverse reference sources name character nativeids character tokens used by the provider to enumerate transcription factors HGNCmap data.frame with atleast two columns, native id as first column and HGNC symbol as second column metadata ANY This class respects the notions that 1) a source of information about transcription factors should have a name, 2) each source has its own native nomenclature for the factors themselves, 3) it is common to use the gene symbol to refer to the transctiption factor, and 4) additional metadata will frequently be required to establish information about provenance of assertions about transcription factors. tfhash tfhash: data.frame with MSigDb TFs, TF targets as symbol or EN- TREZ tfhash: data.frame with MSigDb TFs, TF targets as symbol or ENTREZ tfhash list MSigDb "c3" (motif gene sets) has been harvested for simple annotation of TFs and targets. TFutils::tfhash tfhash[1:3,]

12 12 tftcoll TFtargs gadget to help sort through tags naming TFs gadget to help sort through tags naming TFs TFtargs(gscoll = TFutils::tftColl, inittf = "VDR_Q3", gadtitle = "Search for a TF; its targets will be checked for mapped status in GWAS catalog") gscoll inittf gadtitle a GSEABase GeneSetCollection character(1) initial TF string for app character(1) a title for the gadget panel on app conclusion a data.frame is returned Will use TFutils::gwascat_hg19_chr17 to look for MAPPED_GENE field entries matching targets, also hardcoded to use org.hs.eg.db to map symbols if (interactive()) TFtargs() tftcoll tftcoll: GSEABase GeneSetCollection for transcription factor targets tftcoll: GSEABase GeneSetCollection for transcription factor targets tftcoll GSEABase GeneSetCollection instance run GSEABase::getGMT() on c3/tft geneset collection from MSigDb

13 tftcollmap 13 broad institute TFutils::tftColl tftcollmap tftcollmap: data.frame with information on MSigDb TFs for human tftcollmap: data.frame with information on MSigDb TFs for human tftcollmap data.frame Annotation of TFs is ad-hoc. GeneSet names were tokenized, splitting by underscore, and then fragments were matched to SYMBOL and ALIAS elements of org.hs.eg.db. Extracted March head(tfutils::tftcollmap) URL_s3_tf utility to generate link to biocfound bucket for FIMO TFBS scores utility to generate link to biocfound bucket for FIMO TFBS scores URL_s3_tf(tag = "M3433") tag character(1) token identifying TF, can be an HGNC gene name or Mnnnn PWM tag. It must be findable in TFutils::fimoMap table.

14 14 URL_s3_tf character(1) URL URL_s3_tf

15 Index Topic datasets cisbptfcat, 2 fimo16, 3 fimomap, 3 gwascat_hg19_chr17, 6 hocomoco.mono, 7 metadata_tf, 9 named_tf, 9 tfhash, 11 tftcoll, 12 tftcollmap, 13 tftcollmap, 13 URL_s3_tf, 13 cisbptfcat, 2 fimo16, 3 fimomap, 3 genemodeldf, 4 genemodforgviz, 4 grabtab, 5 gwascat_hg19_chr17, 6 HGNCmap, 6 hocomoco.mono, 7 importfimo (importfimo,tabixfile,granges-method), 7 importfimo,character,missing-method (importfimo,tabixfile,granges-method), 7 importfimo,tabixfile,granges-method, 7 importfimo_local_split, 8 metadata_tf, 9 named_tf, 9 show,tfcatalog-method, 10 TFCatalog, 10 TFCatalog-class, 11 tfhash, 11 TFtargs, 12 tftcoll, 12 15