## ----style, echo = FALSE, results = 'asis'------------------------------------ library(BiocStyle) ## ---- echo = FALSE------------------------------------------------------------ library(knitr) ## ---- results='hide', message=FALSE------------------------------------------- library(decompTumor2Sig) ## ---- message=FALSE, warning=FALSE-------------------------------------------- signatures <- readAlexandrovSignatures() length(signatures) signatures[1] ## ---- eval=FALSE-------------------------------------------------------------- # signatures <- readAlexandrovSignatures(file="") ## ----------------------------------------------------------------------------- # take the example signature flat files provided with decompTumor2Sig sigfiles <- system.file("extdata", paste0("Nik-Zainal_PMID_22608084-pmsignature-sig",1:4,".tsv"), package="decompTumor2Sig") # read the signature flat files signatures <- readShiraishiSignatures(files=sigfiles) signatures[1] ## ----------------------------------------------------------------------------- # load example signatures for breast cancer genomes from Nik-Zainal et al # (PMID: 22608084) in the format produced by pmsignature (PMID: 26630308) pmsigdata <- system.file("extdata", "Nik-Zainal_PMID_22608084-pmsignature-Param.Rdata", package="decompTumor2Sig") load(pmsigdata) # extract the signatures from the pmsignature 'Param' object signatures <- getSignaturesFromEstParam(Param) signatures[1] ## ---- message=FALSE, warning=FALSE-------------------------------------------- sign_a <- readAlexandrovSignatures() sign_s <- convertAlexandrov2Shiraishi(sign_a) sign_s[1] ## ----------------------------------------------------------------------------- isAlexandrovSet(sign_a) isSignatureSet(sign_a) isShiraishiSet(sign_s) isSignatureSet(sign_s) sameSignatureFormat(sign_a, sign_s) ## ----------------------------------------------------------------------------- # load the reference genome and the transcript annotation database refGenome <- BSgenome.Hsapiens.UCSC.hg19::BSgenome.Hsapiens.UCSC.hg19 transcriptAnno <- TxDb.Hsapiens.UCSC.hg19.knownGene::TxDb.Hsapiens.UCSC.hg19.knownGene # take the six breast cancer genomes from Nik-Zainal et al (PMID: 22608084) gfile <- system.file("extdata", "Nik-Zainal_PMID_22608084-VCF-convertedfromMPF.vcf.gz", package="decompTumor2Sig") # read the cancer genomes in VCF format genomes <- readGenomesFromVCF(gfile, numBases=5, type="Shiraishi", trDir=TRUE, refGenome=refGenome, transcriptAnno=transcriptAnno, verbose=FALSE) length(genomes) genomes[1:2] ## ----------------------------------------------------------------------------- # load the reference genome and the transcript annotation database refGenome <- BSgenome.Hsapiens.UCSC.hg19::BSgenome.Hsapiens.UCSC.hg19 transcriptAnno <- TxDb.Hsapiens.UCSC.hg19.knownGene::TxDb.Hsapiens.UCSC.hg19.knownGene # take the six breast cancer genomes from Nik-Zainal et al (PMID: 22608084) gfile <- system.file("extdata", "Nik-Zainal_PMID_22608084-MPF.txt.gz", package="decompTumor2Sig") # read the cancer genomes in MPF format genomes <- readGenomesFromMPF(gfile, numBases=5, type="Shiraishi", trDir=TRUE, refGenome=refGenome, transcriptAnno=transcriptAnno, verbose=FALSE) ## ----------------------------------------------------------------------------- # get breast cancer genomes from Nik-Zainal et al (PMID: 22608084) # in the format produced by pmsignature (PMID: 26630308) pmsigdata <- system.file("extdata", "Nik-Zainal_PMID_22608084-pmsignature-G.Rdata", package="decompTumor2Sig") load(pmsigdata) # extract the genomes from the pmsignature 'G' object genomes <- getGenomesFromMutFeatData(G, normalize=TRUE) genomes[1] ## ---- message=FALSE----------------------------------------------------------- # load the reference genome and the transcript annotation database refGenome <- BSgenome.Hsapiens.UCSC.hg19::BSgenome.Hsapiens.UCSC.hg19 transcriptAnno <- TxDb.Hsapiens.UCSC.hg19.knownGene::TxDb.Hsapiens.UCSC.hg19.knownGene # take six breast cancer genomes from Nik-Zainal et al (PMID: 22608084) gfile <- system.file("extdata", "Nik-Zainal_PMID_22608084-VCF-convertedfromMPF.vcf.gz", package="decompTumor2Sig") # get the corresponding VRanges object (using the VariantAnnotation package) library(VariantAnnotation) vr <- readVcfAsVRanges(gfile, genome="hg19") # convert the VRanges object to the decompTumor2Sig format genomes <- convertGenomesFromVRanges(vr, numBases=5, type="Shiraishi", trDir=TRUE, refGenome=refGenome, transcriptAnno=transcriptAnno, verbose=FALSE) ## ----------------------------------------------------------------------------- signatures <- readAlexandrovSignatures() plotMutationDistribution(signatures[[1]]) ## ----------------------------------------------------------------------------- sigfiles <- system.file("extdata", paste0("Nik-Zainal_PMID_22608084-pmsignature-sig",1:4,".tsv"), package="decompTumor2Sig") signatures <- readShiraishiSignatures(files=sigfiles) plotMutationDistribution(signatures[[1]]) ## ---- echo=FALSE-------------------------------------------------------------- include_graphics("example-sign-Shiraishi.png") ## ----------------------------------------------------------------------------- refGenome <- BSgenome.Hsapiens.UCSC.hg19::BSgenome.Hsapiens.UCSC.hg19 gfile <- system.file("extdata", "Nik-Zainal_PMID_22608084-VCF-convertedfromMPF.vcf.gz", package="decompTumor2Sig") genomes <- readGenomesFromVCF(gfile, numBases=3, type="Alexandrov", trDir=FALSE, refGenome=refGenome, verbose=FALSE) plotMutationDistribution(genomes[[1]]) ## ----------------------------------------------------------------------------- # load the 15 Shiraishi signatures obtained from # 435 tumor genomes from Alexandrov et al. sfile <- system.file("extdata", "Alexandrov_PMID_23945592_435_tumors-pmsignature-15sig.Rdata", package="decompTumor2Sig") load(sfile) length(signatures) signatures[1] ## ----------------------------------------------------------------------------- # load the reference genome and the transcript annotation database refGenome <- BSgenome.Hsapiens.UCSC.hg19::BSgenome.Hsapiens.UCSC.hg19 transcriptAnno <- TxDb.Hsapiens.UCSC.hg19.knownGene::TxDb.Hsapiens.UCSC.hg19.knownGene # take six breast cancer genomes from Nik-Zainal et al (PMID: 22608084) gfile <- system.file("extdata", "Nik-Zainal_PMID_22608084-VCF-convertedfromMPF.vcf.gz", package="decompTumor2Sig") # read the cancer genomes in VCF format genomes <- readGenomesFromVCF(gfile, numBases=5, type="Shiraishi", trDir=TRUE, refGenome=refGenome, transcriptAnno=transcriptAnno, verbose=FALSE) ## ---- fig.asp=1--------------------------------------------------------------- plotExplainedVariance(genomes[[1]], signatures, minExplainedVariance=0.9, minNumSignatures=2, maxNumSignatures=NULL, greedySearch=TRUE) ## ----------------------------------------------------------------------------- exposure <- decomposeTumorGenomes(genomes[1], signatures) ## ----------------------------------------------------------------------------- exposure ## ---- message=FALSE, warning=FALSE, fig.asp=1--------------------------------- plotDecomposedContribution(exposure) ## ----------------------------------------------------------------------------- exposures <- decomposeTumorGenomes(genomes, signatures) length(exposures) exposures[1:2] ## ----------------------------------------------------------------------------- isExposureSet(exposures) ## ----------------------------------------------------------------------------- exposures <- decomposeTumorGenomes(genomes[1], signatures, minExplainedVariance=0.9, minNumSignatures=2, maxNumSignatures=NULL, greedySearch=FALSE, verbose=TRUE) ## ----------------------------------------------------------------------------- exposures ## ---- fig.asp=1--------------------------------------------------------------- plotDecomposedContribution(exposures[[1]]) ## ---- fig.asp=1--------------------------------------------------------------- exposures <- decomposeTumorGenomes(genomes[1], signatures, minExplainedVariance=0.95, minNumSignatures=2, maxNumSignatures=NULL, greedySearch=TRUE, verbose=TRUE) exposures plotDecomposedContribution(exposures[[1]]) ## ---- echo=FALSE-------------------------------------------------------------- # load the reference genome and the transcript annotation database refGenome <- BSgenome.Hsapiens.UCSC.hg19::BSgenome.Hsapiens.UCSC.hg19 transcriptAnno <- TxDb.Hsapiens.UCSC.hg19.knownGene::TxDb.Hsapiens.UCSC.hg19.knownGene # take the 15 Shiraishi signatures obtained from # 435 tumor genomes from Alexandrov et al. sfile <- system.file("extdata", "Alexandrov_PMID_23945592_435_tumors-pmsignature-15sig.Rdata", package="decompTumor2Sig") load(sfile) gfile <- system.file("extdata", "Nik-Zainal_PMID_22608084-VCF-convertedfromMPF.vcf.gz", package="decompTumor2Sig") # read the cancer genomes in VCF format genomes <- readGenomesFromVCF(gfile, numBases=5, type="Shiraishi", trDir=TRUE, refGenome=refGenome, transcriptAnno=transcriptAnno, verbose=FALSE) ## ----------------------------------------------------------------------------- exposures <- decomposeTumorGenomes(genomes, signatures) computeExplainedVariance(exposures, signatures, genomes) ## ----------------------------------------------------------------------------- genomes_predicted <- composeGenomesFromExposures(exposures, signatures) genomes_predicted[1:2] ## ----------------------------------------------------------------------------- evaluateDecompositionQuality(exposures[[1]], signatures, genomes[[1]], plot=FALSE) ## ---- fig.asp=1--------------------------------------------------------------- evaluateDecompositionQuality(exposures[[1]], signatures, genomes[[1]], plot=TRUE) ## ----------------------------------------------------------------------------- # get 4 Shiraishi signatures from 21 breast cancers from # Nik-Zainal et al (PMID: 22608084) sigfiles <- system.file("extdata", paste0("Nik-Zainal_PMID_22608084-pmsignature-sig",1:4,".tsv"), package="decompTumor2Sig") sign_s4 <- readShiraishiSignatures(files=sigfiles) # get 15 Shiraishi signatures obtained from # 435 tumor genomes from Alexandrov et al. sfile <- system.file("extdata", "Alexandrov_PMID_23945592_435_tumors-pmsignature-15sig.Rdata", package="decompTumor2Sig") load(sfile) sign_s15 <- signatures ## ----------------------------------------------------------------------------- determineSignatureDistances(fromSignature=sign_s4[[1]], toSignatures=sign_s15, method="frobenius") ## ----------------------------------------------------------------------------- mapSignatureSets(fromSignatures=sign_s4, toSignatures=sign_s15, method="frobenius", unique=FALSE) ## ---- message=FALSE, warning=FALSE-------------------------------------------- sign_a <- readAlexandrovSignatures() sign_a2s <- convertAlexandrov2Shiraishi(sign_a) ## ----------------------------------------------------------------------------- sign_sdown <- downgradeShiraishiSignatures(sign_s15, numBases=3, removeTrDir=TRUE) sign_s15[1] sign_sdown[1] ## ----------------------------------------------------------------------------- mapSignatureSets(fromSignatures=sign_sdown, toSignatures=sign_a2s, method="frobenius", unique=TRUE)