Hi Kasper, I was wondering if you have any additional thoughts on the warning message below that you said "does not look nice." Any idea where it came from, how to fix it, or whether it matters? I'd really like to use bumphunter, if possible. Thanks again! Allegra _________________________________ Allegra A. Petti, Ph.D. The Genome Institute 4444 Forest Park Ave. St. Louis, MO 63108 apetti@genome.wustl.edu allegra.conbrio@post.harvard.edu On Feb 25, 2014, at 10:43 AM, Kasper Daniel Hansen <khansen@jhsph.edu> wrote: > This does not look nice: > > Warning message: > In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > > I don't think the warnings > > Could not infer array name for file: > > are troublesome, but it is hard to read your output. > > Do you have the right number of samples in data.grs object? > > Kasper > > > On Tue, Feb 25, 2014 at 11:35 AM, Allegra Petti <apetti@genome.wustl.edu> wrote: > Kasper, > > Thanks for your message and the further clarification. I will try using > the additional parameters you mentioned. To answer your question, I only > have 56 samples, and the size of data.grs is 237.1 Mb. I get some > additional warning messages that I'm including again (below) in case > they are informative. > > Best, > Allegra > ____________________________________________________________________ ___________ > From standard err: > > Warning messages: > 1: In > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/ IdatSampleSheet.csv", > : > Could not infer array name for file: > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/IdatSam pleSheet.csv > 2: In > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/ IdatSampleSheet.csv", > : > Could not infer slide name for file: > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/IdatSam pleSheet.csv > 3: In > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/ IdatSampleSheet.csv", > : > Could not infer array name for file: > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/SampleS heet140219.csv > 4: In > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/ IdatSampleSheet.csv", > : > Could not infer slide name for file: > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/SampleS heet140219.csv > [bumphunterEngine] Parallelizing using 12 workers/cores (backend: > doParallel, version: 1.0.6). > [bumphunterEngine] Computing coefficients. > [bumphunterEngine] Performing 100 permutations. > [bumphunterEngine] Computing marginal permutation p-values. > [bumphunterEngine] cutoff: 0.95 > [bumphunterEngine] Finding regions. > [bumphunterEngine] Found 6278 bumps. > [bumphunterEngine] Computing regions for each permutation. > > Warning messages: > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 2: In FUN(newX[, i], ...) : NAs found and removed. ind changed. > 3: In FUN(newX[, i], ...) : NAs found and removed. ind changed. > 4: In FUN(newX[, i], ...) : NAs found and removed. ind changed. > > > > > > > Warning message: > Warning messages: > Warning messages: > Warning messages: > > Warning messages: > Warning messages: > > In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > Warning messages: > beta2dmr.140224.err lines 84-106/115 92% > > > > > > > Warning message: > Warning messages: > Warning messages: > Warning messages: > > Warning messages: > Warning messages: > > In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > Warning messages: > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > 1: In regionFinder(x = beta, chr = chr, pos = pos, cluster = cluster, : > NAs found and removed. ind changed. > > > Warning messages: > 2: In FUN(newX[, i], ...) : NAs found and removed. ind changed. > Execution halted > ____________________________________________________________________ _________________ > From standard output: > > ------------------------------------------------------------ > Sender: LSF System <lsfadmin@blade14-2-15.gsc.wustl.edu> > Subject: Job 5344099: <beta2dmr> Exited > > Job <beta2dmr> was submitted from host <linus2091.gsc.wustl.edu> by user > <apetti> in cluster <lsfcluster1>. > Job was executed on host(s) <12*blade14-2-15.gsc.wustl.edu>, in queue > <long>, as user <apetti> in cluster <lsfcluster1>. > </gscuser> was used as the home directory. > </gscuser> was used as the working directory. > Started at Mon Feb 24 16:28:45 2014 > Results reported at Mon Feb 24 16:36:30 2014 > > Your job looked like: > > ------------------------------------------------------------ > # LSBATCH: User input > ~/gsc/R3.0.2/bin/Rscript beta2dmr_140220.r > ------------------------------------------------------------ > > TERM_MEMLIMIT: job killed after reaching LSF memory usage limit. > Exited with exit code 1. > > Resource usage summary: > > CPU time : 762.28 sec. > Max Memory : 69236 MB > Max Swap : 71263 MB > > Max Processes : 15 > Max Threads : 15 > > > On 02/24/2014 07:00 PM, Kasper Daniel Hansen wrote: > > One clarification: Jim's interpretation is for qCutoff. The cutoff > > argument is the actual cutoff. The call you are making says that any > > difference greater than 0.05 on the M scale is a possible bump. You > > can see from the output that there more than half the array inside a > > candidate bump. You probably want qCutoff or set type="Beta" or set > > cutoff to something bigger. > > > > This is really our fault for providing insanely crappy defaults. I > > will discuss with co-authors and we will change this. > > > > However, I am not sure I understand the memory blow up. How many > > samples do you have? What is the output of > > print(object.size(getBeta(data.grs)), units = "auto") > > > > Kasper > > > > > > On Mon, Feb 24, 2014 at 2:40 PM, Allegra A. Petti > > <apetti@genome.wustl.edu <mailto:apetti@genome.wustl.edu="">> wrote: > > > > Ah - thank you very much for the clarification!! I used 0.05 > > rather mindlessly because that's what the tutorial used. > > > > Best, > > Allegra > > _________________________________ > > Allegra A. Petti, Ph.D. > > > > The Genome Institute > > 4444 Forest Park Ave. > > St. Louis, MO 63108 > > apetti@genome.wustl.edu <mailto:apetti@genome.wustl.edu> > > allegra.conbrio@post.harvard.edu > > <mailto:allegra.conbrio@post.harvard.edu> > > > > On Feb 24, 2014, at 1:37 PM, "James W. MacDonald" <jmacdon@uw.edu> > <mailto:jmacdon@uw.edu>> wrote: > > > > > Hi Allegra, > > > > > > > > > On 2/24/2014 1:41 PM, Allegra Petti [guest] wrote: > > >> Dear All, > > >> > > >> I am trying to identify Differentially Methylated Regions > > (DMRs) using a tab-delimited file of beta values obtained with > > Illumina's 450k methylation arrays. I am using minfi and its > > implementation of bumphunter (development version 1.9.11). > > >> > > >> However, I run out of memory when I use a mere 100 > > permutations, and have tried different amounts of memory to no > > avail. Of further concern is the fact that the bumphunter > > reference (Jaffe, et al (2011) International J. of Epidemiology: > > 41:200-209) states that each permutation takes two hours (see p. > > 205). At that rate, a standard run with 1000 permutations would > > take over 83 days. > > >> > > >> My questions are as follows (code and output included below): > > >> 1. Is there a better way to run minfi/bumphunter, or specific > > resources I should allocate? (I am currently using parallel > > processing with four cores, and have tried various amounts of memory.) > > >> 2. Does minfi/bumphunter include a non-permutation-based method > > for estimating statistical significance? Jaffe et al state that > > they implemented a second, faster, p-value calculation following > > the method of Effron and Tibshirani (see p. 205). Does anyone know > > if this method is implemented in minfi? > > >> 3. Is there a better method for identifying DMRs? (I am also > > experimenting with methyAnalysis, which has nice visualization > > options, but (a) is poorly documented and (b) surprisingly found > > no DMRs in my data set using default settings.) > > >> > > >> Many thanks in advance for any insight and/or suggestions! > > >> > > >> Sincerely, > > >> Allegra > > >> _________________________________________________________________ > > >> Code: > > >> > > >> # This R script reads in a tab-delimited matrix of Beta values > > (with a header line) > > >> # and finds differentially-methylated regions using minfi > > >> > > >> # sample command: bsub -oo beta2dmr.140224.out -e > > beta2dmr.140224.err -q long -M 16000000 -R 'select[type==LINUX64 > > && mem>16000] span[hosts=1] rusage[mem=16000]' -n 4 -J beta2dmr > > "~/gsc/R3.0.2/bin/Rscript beta2dmr_140220.r" > > >> > > >> library(minfi); # currently requires development version 1.9.11 > > >> library(IlluminaHumanMethylation450kanno.ilmn12.hg19); # Note: > > had to be installed manually > > >> library(foreach); # used for parallel processing > > >> library(doRNG); # is this actually used?? > > >> library(doParallel); # "backend" for foreach package > > >> registerDoParallel(cores = 4); > > >> > > >> #betas.frame <- > > read.table(file="testbetas.txt",sep="\t",header=TRUE,na.string s=c(NA),row.names=1,quote=""); > > >> betas.frame <- > > read.table(file="betas_140220.txt",sep="\t",header=TRUE,na.str ings=c(NA),row.names=1,quote=""); > > >> betas <- as.matrix(betas.frame); # convert data frame to matrix > > >> data.rs <http: data.rs=""> <- RatioSet(Beta = > > betas,annotation=c(array= "IlluminaHumanMethylation450k", > > annotation = "ilmn12.hg19")); # create RatioSet > > >> data.grs <- mapToGenomedata.rs <http: data.rs="">); # create > > GenomicRatioSet > > >> sampleNamesdata.rs <http: data.rs="">); # display the sample > > names (ie column headings) > > >> targets <- > > read.450k.sheet('/gscmnt/gc3016/info/medseq/apetti/AMLrefracto ry/dmr.analysis',recursive=FALSE); > > # read Sample Sheet > > >> samples <- sampleNamesdata.rs <http: data.rs="">); # get sample > > names (ie column headers) from input file of beta values > > >> j <- match(samples,targets$Sample); # get row indices from > > sample sheet that correspond to sample names (column headers) in > > beta value input file > > >> pheno <- targets$Sample_Group[j]; # extract corresponding > > phenotype (e.g. "tumor" or "normal") from Sample_Group column of > > Sample Sheet > > >> designMatrix <- model.matrix(~ pheno); # specify design matrix > > for regression > > >> dmr <- bumphunter(data.grs, design = designMatrix, cutoff = > > 0.05, B=100); # run bumphunter with B permutations > > > > > > That's your problem ^^^^^^^^^^^^^^^^^^^^ > > > > > > You can interpret the cutoff argument this way; 'Select the > > bumps that are larger than the Xth quantile of all bumps in my > > data set'. By using 0.05, you are selecting almost all of the > > bumps in your data, which is not what you want to do. > > > > > > Instead, you want to use a cutoff of 0.95 or 0.99, which is > > 'Select the bumps that are larger than 95% or 99% of all the bumps > > in my data'. Or to put it another way, you want to select the > > bumps that are big enough that they are likely to represent > > differential methylation, and ignore all the little bumps that > > likely arise by chance alone. > > > > > > Best, > > > > > > Jim > > > > > > > > >> save(dmr, file="dmr.minfi.100_140222"); > > >> > > >> __________________________________________________________________ > > >> Standard Output: > > >> > > >> [1] "TCGA.AB.2940.03A.01D.0742.05" "TCGA.AB.2944.03A.01D.0743.05" > > >> [3] "TCGA.AB.2866.03A.01D.0741.05" "TCGA.AB.2871.03A.01D.0742.05" > > >> [5] "TCGA.AB.2934.03A.01D.0743.05" "TCGA.AB.2807.03A.01D.0741.05" > > >> [7] "TCGA.AB.2809.03A.01D.0741.05" "TCGA.AB.2984.03A.01D.0742.05" > > >> [9] "TCGA.AB.2921.03A.01D.0743.05" "TCGA.AB.2952.03A.01D.0742.05" > > >> [11] "TCGA.AB.2829.03A.01D.0741.05" "TCGA.AB.2901.03A.01D.0742.05" > > >> [13] "TCGA.AB.2827.03A.01D.0741.05" "TCGA.AB.2884.03A.01D.0742.05" > > >> [15] "TCGA.AB.3011.03A.01D.0742.05" "TCGA.AB.2878.03A.01D.0742.05" > > >> [17] "TCGA.AB.2933.03A.01D.0742.05" "TCGA.AB.2843.03A.01D.0741.05" > > >> [19] "TCGA.AB.2814.03A.01D.0741.05" "TCGA.AB.2856.03A.01D.0741.05" > > >> [21] "TCGA.AB.2855.03A.01D.0741.05" "TCGA.AB.2919.03A.01D.0743.05" > > >> [23] "TCGA.AB.2967.03A.01D.0742.05" "TCGA.AB.2817.03A.01D.0742.05" > > >> [25] "TCGA.AB.2887.03A.01D.0742.05" "TCGA.AB.2894.03A.01D.0742.05" > > >> [27] "TCGA.AB.2895.03A.01D.0742.05" "TCGA.AB.2947.03A.01D.0743.05" > > >> [29] "TCGA.AB.2930.03A.01D.0743.05" "TCGA.AB.2896.03A.01D.0742.05" > > >> [31] "TCGA.AB.2983.03A.01D.0742.05" "TCGA.AB.2945.03A.01D.0741.05" > > >> [33] "TCGA.AB.2918.03A.01D.0743.05" "TCGA.AB.2928.03A.01D.0743.05" > > >> [35] "TCGA.AB.2979.03A.01D.0742.05" "TCGA.AB.2969.03A.01D.0741.05" > > >> [37] "TCGA.AB.2891.03A.01D.0742.05" "TCGA.AB.2971.03A.01D.0741.05" > > >> [39] "TCGA.AB.2964.03A.01D.0741.05" "TCGA.AB.2835.03A.01D.0741.05" > > >> [41] "TCGA.AB.3002.03A.01D.0742.05" "TCGA.AB.2853.03A.01D.0741.05" > > >> [43] "TCGA.AB.2836.03A.01D.0741.05" "TCGA.AB.2909.03A.01D.0743.05" > > >> [45] "TCGA.AB.2932.03A.01D.0743.05" "TCGA.AB.2926.03A.01D.0742.05" > > >> [47] "TCGA.AB.2826.03A.01D.0741.05" "TCGA.AB.2911.03A.01D.0741.05" > > >> [49] "TCGA.AB.2920.03A.01D.0742.05" "TCGA.AB.2917.03A.01D.0741.05" > > >> [51] "TCGA.AB.2869.03A.01D.0742.05" "TCGA.AB.2873.03A.01D.0742.05" > > >> [53] "TCGA.AB.2879.03A.01D.0742.05" "TCGA.AB.2831.03A.01D.0741.05" > > >> [55] "TCGA.AB.2816.03A.01D.0742.05" "TCGA.AB.2990.03A.01D.0742.05" > > >> [read.450k.sheet] Found the following CSV files: > > >> [1] > > "/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/ IdatSampleSheet.csv" > > >> [2] > > "/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/ SampleSheet140219.csv" > > >> > > >> ------------------------------------------------------------ > > >> Sender: LSF System <lsfadmin@blade14-4-11.gsc.wustl.edu> > <mailto:lsfadmin@blade14-4-11.gsc.wustl.edu>> > > >> Subject: Job 5329542: <beta2dmr> Exited > > >> > > >> Job <beta2dmr> was submitted from host <linus2091.gsc.wustl.edu> > <http: linus2091.gsc.wustl.edu="">> by user <apetti> in cluster > > <lsfcluster1>. > > >> Job was executed on host(s) <4*blade14-4-11.gsc.wustl.edu > > <http: blade14-4-11.gsc.wustl.edu="">>, in queue <long>, as user > > <apetti> in cluster <lsfcluster1>. > > >> </gscuser> was used as the home directory. > > >> > > >> __________________________________________________________________ > > >> Standard Error: > > >> > > >> Loading required package: methods > > >> Loading required package: BiocGenerics > > >> Loading required package: parallel > > >> > > >> Attaching package: 'BiocGenerics' > > >> > > >> The following objects are masked from 'package:parallel': > > >> > > >> clusterApply, clusterApplyLB, clusterCall, clusterEvalQ, > > >> clusterExport, clusterMap, parApply, parCapply, parLapply, > > >> parLapplyLB, parRapply, parSapply, parSapplyLB > > >> > > >> The following object is masked from 'package:stats': > > >> > > >> xtabs > > >> > > >> The following objects are masked from 'package:base': > > >> > > >> Filter, Find, Map, Position, Reduce, anyDuplicated, append, > > >> as.data.frame, as.vector, cbind, colnames, duplicated, > > eval, evalq, > > >> get, intersect, is.unsorted, lapply, mapply, match, mget, > > order, > > >> paste, pmax, pmax.int <http: pmax.int="">, pmin, pmin.int > > <http: pmin.int="">, rank, rbind, rep.int <http: rep.int="">, > > >> rownames, sapply, setdiff, sort, table, tapply, union, unique, > > >> unlist > > >> > > >> Loading required package: Biobase > > >> Welcome to Bioconductor > > >> > > >> Vignettes contain introductory material; view with > > >> 'browseVignettes()'. To cite Bioconductor, see > > >> 'citation("Biobase")', and for packages 'citation("pkgname")'. > > >> > > >> Loading required package: lattice > > >> Loading required package: GenomicRanges > > >> Loading required package: IRanges > > >> Loading required package: XVector > > >> Loading required package: Biostrings > > >> Loading required package: bumphunter > > >> Loading required package: foreach > > >> Loading required package: iterators > > >> Loading required package: locfit > > >> locfit 1.5-9.1 2013-03-22 > > >> > > >> Attaching package: 'locfit' > > >> > > >> The following objects are masked from 'package:GenomicRanges': > > >> > > >> left, right > > >> > > >> Loading required package: rngtools > > >> Loading required package: pkgmaker > > >> Loading required package: registry > > >> > > >> Attaching package: 'pkgmaker' > > >> > > >> The following object is masked from 'package:IRanges': > > >> > > >> new2 > > >> > > >> Warning messages: > > >> 1: In > > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.ana lysis/IdatSampleSheet.csv", > > : > > >> Could not infer array name for file: > > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/I datSampleSheet.csv > > >> 2: In > > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.ana lysis/IdatSampleSheet.csv", > > : > > >> Could not infer slide name for file: > > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/I datSampleSheet.csv > > >> 3: In > > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.ana lysis/IdatSampleSheet.csv", > > : > > >> Could not infer array name for file: > > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/S ampleSheet140219.csv > > >> 4: In > > FUN(c("/gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.ana lysis/IdatSampleSheet.csv", > > : > > >> Could not infer slide name for file: > > /gscmnt/gc3016/info/medseq/apetti/AMLrefractory/dmr.analysis/S ampleSheet140219.csv > > >> [bumphunterEngine] Parallelizing using 4 workers/cores > > (backend: doParallel, version: 1.0.6). > > >> [bumphunterEngine] Computing coefficients. > > >> [bumphunterEngine] Performing 100 permutations. > > >> [bumphunterEngine] Computing marginal permutation p-values. > > >> [bumphunterEngine] cutoff: 0.05 > > >> [bumphunterEngine] Finding regions. > > >> [bumphunterEngine] Found 233469 bumps. > > >> [bumphunterEngine] Computing regions for each permutation. > > >> > > >> Warning message: > > >> In regionFinder(x = beta, chr = chr, pos = pos, cluster = > > cluster, : > > >> NAs found and removed. ind changed. > > >> Execution halted > > >> > > >> > > >> -- output of sessionInfo(): > > >> > > >> R version 3.0.2 (2013-09-25) > > >> Platform: x86_64-unknown-linux-gnu (64-bit) > > >> > > >> locale: > > >> [1] LC_CTYPE=en_US.utf8 LC_NUMERIC=C > > >> [3] LC_TIME=en_US.utf8 LC_COLLATE=C > > >> [5] LC_MONETARY=en_US.utf8 LC_MESSAGES=en_US.utf8 > > >> [7] LC_PAPER=en_US.utf8 LC_NAME=C > > >> [9] LC_ADDRESS=C LC_TELEPHONE=C > > >> [11] LC_MEASUREMENT=en_US.utf8 LC_IDENTIFICATION=C > > >> > > >> attached base packages: > > >> [1] parallel stats graphics grDevices utils datasets > > methods > > >> [8] base > > >> > > >> other attached packages: > > >> [1] doParallel_1.0.6 > > >> [2] doRNG_1.5.5 > > >> [3] rngtools_1.2.3 > > >> [4] pkgmaker_0.17.4 > > >> [5] registry_0.2 > > >> [6] IlluminaHumanMethylation450kanno.ilmn12.hg19_0.2.1 > > >> [7] minfi_1.9.11 > > >> [8] bumphunter_1.2.0 > > >> [9] locfit_1.5-9.1 > > >> [10] iterators_1.0.6 > > >> [11] foreach_1.4.1 > > >> [12] Biostrings_2.30.1 > > >> [13] GenomicRanges_1.14.4 > > >> [14] XVector_0.2.0 > > >> [15] IRanges_1.20.6 > > >> [16] lattice_0.20-24 > > >> [17] Biobase_2.22.0 > > >> [18] BiocGenerics_0.8.0 > > >> > > >> loaded via a namespace (and not attached): > > >> [1] AnnotationDbi_1.24.0 DBI_0.2-7 MASS_7.3-29 > > >> [4] R.methodsS3_1.6.1 RColorBrewer_1.0-5 RSQLite_0.11.4 > > >> [7] XML_3.98-1.1 annotate_1.40.0 beanplot_1.1 > > >> [10] codetools_0.2-8 digest_0.6.4 genefilter_1.44.0 > > >> [13] grid_3.0.2 illuminaio_0.2.0 itertools_0.1-1 > > >> [16] limma_3.18.4 matrixStats_0.8.14 mclust_4.2 > > >> [19] multtest_2.18.0 nlme_3.1-113 nor1mix_1.1-4 > > >> [22] preprocessCore_1.24.0 reshape_0.8.4 siggenes_1.36.0 > > >> [25] splines_3.0.2 stats4_3.0.2 stringr_0.6.2 > > >> [28] survival_2.37-7 tools_3.0.2 xtable_1.7-1 > > >> > > >> -- > > >> Sent via the guest posting facility at bioconductor.org > > <http: bioconductor.org="">. > > >> > > >> _______________________________________________ > > >> Bioconductor mailing list > > >> Bioconductor@r-project.org <mailto:bioconductor@r-project.org> > > >> https://stat.ethz.ch/mailman/listinfo/bioconductor > > >> Search the archives: > > http://news.gmane.org/gmane.science.biology.informatics.conductor > > > > > > -- > > > James W. 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