Package ClusterSignificance

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Package ClusterSignificance May 11, 2018 Title The ClusterSignificance package provides tools to assess if class clusters in dimensionality reduced data representations have a separation different from permuted data Version 1.8.0 Author Jason T. Serviss [aut, cre], Jesper R. Gadin [aut] Maintainer Jason T Serviss <jason.serviss@ki.se> The ClusterSignificance package provides tools to assess if class clusters in dimensionality reduced data representations have a separation different from permuted data. The term class clusters here refers to, clusters of points representing known classes in the data. This is particularly useful to determine if a subset of the variables, e.g. genes in a specific pathway, alone can separate samples into these established classes. ClusterSignificance accomplishes this by, projecting all points onto a one dimensional line. Cluster separations are then scored and the probability of the seen separation being due to chance is evaluated using a permutation method. Depends R (>= 3.3.0) URL https://github.com/jasonserviss/clustersignificance/ BugReports https://github.com/jasonserviss/clustersignificance/issues Imports methods, pracma, princurve, scatterplot3d, RColorBrewer, grdevices, graphics, utils, stats License GPL-3 LazyData true Suggests knitr, rmarkdown, testthat, BiocStyle, ggplot2, plsgenomics, covr VignetteBuilder knitr biocviews Clustering, Classification, PrincipalComponent, StatisticalMethod NeedsCompilation no Collate 'ClusterSignificance-package.R' 'All-classes.R' 'classifier-methods.r' 'initialize-methods.r' 'mlpmatrix.r' 'pcpmatrix.r' 'permutation-methods.r' 'plot-methods.r' 'projection-methods.r' 'show-methods.r' 1

2 ClusterSignificance-package RoxygenNote 6.0.1 R topics documented: ClusterSignificance-package................................ 2 ClassifiedPoints-class.................................... 3 Mlp-class.......................................... 4 mlpmatrix.......................................... 6 Pcp-class.......................................... 7 pcpmatrix.......................................... 8 PermutationResults-class.................................. 9 Index 12 ClusterSignificance-package The ClusterSignificance package provides tools to assess if clusters have a separation different from random or permuted data. Details The ClusterSignificance package provides tools to assess if clusters have a separation different from random or permuted data. ClusterSignificance investigates clusters of two or more groups by first, projecting all points onto a one dimensional line. Cluster separations are then scored and the probability of the seen separation being due to chance is evaluated using a permutation method. Package: ClusterSignificance Type: Package Version: 1.0 Date: 2016-02-28 License: GPL-3 Author(s) Author: Jason T. Serviss, Jesper R. Gadin References Reference to published application note (work in progress)

ClassifiedPoints-class 3 ClassifiedPoints-class Classification of the one dimensional points in a Pcp or Mlp object. Classification based on ROC params (TN TP FP FN). Usage ## S4 method for signature 'ClassifiedPoints' getdata(x, n = NULL) classify(x,...) ## S4 method for signature 'Pcp' classify(x,...) ## S4 method for signature 'Mlp' classify(x,...) ## S4 method for signature 'ClassifiedPoints' initialize(.object,..., scores, scores.points = scores.points, scores.index = scores.index, ROC, AUC, class.color) ## S4 method for signature 'ClassifiedPoints,missing' plot(x, y, comparison = "all", class.color = NULL,...) ## S4 method for signature 'ClassifiedPoints' show(object) Arguments x n Pcp or Mlp Object for the function classify otherwise it is a ClassifiedPoints object data to extract from ClassifiedPoints (NULL gives all)... additional arguments to pass on.object scores scores.points scores.index ROC AUC class.color y comparison object internal object final scores sorted points index of sorted points parameters (TN, TP, FN and FP) area under the curve user assigned group coloring scheme default plot param, which should be set to NULL Specify a comparison i.e. ("grp1 vs grp2") and plot only that comparison. ClassifiedPoints Object

4 Mlp-class Details Value Tests all possible discrimination lines and picks the one with highest score based on a score which is simply calculated by the formula (TP - FP) + (TN - FN). The plot shows the distribution of scores for different discrimination lines. Each line is a separator that has a score for the separation of the two groups, and the height of the line marks the score for this separation. The classify function returns an object of class ClassifiedPoints Author(s) Jesper R. Gadin and Jason T. Serviss Examples #use demo data data(pcpmatrix) classes <- rownames(pcpmatrix) #run function prj <- pcp(pcpmatrix, classes) cl <- classify(prj) #getdata accessor getdata(cl) #getdata accessor specific getdata(cl, "scores") #plot result plot(cl) Mlp-class Projection of points into one dimension. Usage Project points onto the mean based line. ## S4 method for signature 'Mlp' getdata(x, n = NULL) ## S4 method for signature 'Mlp' initialize(.object,..., classes, points.orig, line, points.onedim, class.color)

Mlp-class 5 ## S4 method for signature 'Mlp,missing' plot(x, y, steps = "all",...) mlp(mat,...) ## S4 method for signature 'matrix' mlp(mat, classes, class.color = NULL,...) ## S4 method for signature 'Mlp' show(object) Arguments x n.object matrix object for the function mlp otherwise it is a Mlp object data to extract from Mlp (NULL gives all) internal object... additional arguments to pass on classes points.orig line points.onedim class.color y steps mat object vector in same order as rows in matrix multidimensional points describing the original data multidimensional points describing a line a vector of points user assigned group coloring scheme default plot param, which should be set to NULL(default: NULL) 1,2,3,4,5,6 or "all" matrix with samples on rows, PCs in columns. Ordered PCs, with PC1 to the left. Mlp object Details Projection of the points onto a line between the mean of two groups. Mlp is the abbreviation for mean line projection. The function accepts, at the moment, only two groups and two PCs at a time. An object containing results from a mean line projection reduction to one dimension. The group and the one dimensional points are the most important information to carry out a classification using the classify() function. As a help to illustrate the details of the dimension reduction, the information from some critical steps are stored in the object. To visually explore these there is a dedicated plot method for Mlp objects, use plot(). Value The mlp function returns an object of class Mlp Author(s) Jesper R. Gadin and Jason T. Serviss

6 mlpmatrix Examples #use demo data data(mlpmatrix) groups <- rownames(mlpmatrix) #run function prj <- mlp(mlpmatrix, groups) #getdata accessor getdata(prj) #getdata accessor specific getdata(prj, "line") #plot result plot(prj) mlpmatrix Simulated data used to demonstrate the Mlp method. Mlp demonstration matrix. Usage mlpmatrix Format Matrix rownames Groups colnames dimension number Value simulated matrix Examples mlpmatrix

Pcp-class 7 Pcp-class Projection of points into one dimension. Usage Project points onto a principal curve. getdata(x,...) ## S4 method for signature 'Pcp' getdata(x, n = NULL) ## S4 method for signature 'Pcp' initialize(.object,..., classes, points.orig, line, points.onedim, index, class.color) ## S4 method for signature 'Pcp,missing' plot(x, y, steps = "all", class.color = NULL,...) pcp(mat,...) ## S4 method for signature 'matrix' pcp(mat, classes, df = NULL, warn = TRUE, class.color = NULL,...) ## S4 method for signature 'Pcp' show(object) Arguments x matrix object for the function pcp otherwise it is a Pcp object... additional arguments to pass on n.object classes points.orig line points.onedim index class.color y steps mat df data to extract from Pcp (NULL gives all) internal object vector in same order as rows in matrix multidimensional points describing the original data multidimensional points describing a line a vector of points internal index from the projection user assigned group coloring scheme default plot param, which should be set to NULL 1,2,3,4,5,6 or "all" matrix with samples on rows, PCs in columns. Ordered PCs, with PC1 to the left. degrees of freedom, passed to smooth.spline

8 pcpmatrix warn object logical indicating if a change in the default df argument should generate a warning. mostly for internal use. Pcp object Details Value The resulting Pcp object containing results from a principal curve reduction to one dimension. The group and the one dimensional points will be the information needed to carry out a classification using the classify() function. As a help to illustrate the details of the dimension reduction, the information from some critical steps is stored in the object. To visually explore these there is a dedicated plot method for Pcp objects, use plot(). The pcp function returns an object of class Pcp Author(s) Jesper R. Gadin and Jason T. Serviss Examples #use demo data data(pcpmatrix) classes <- rownames(pcpmatrix) #run function prj <- pcp(pcpmatrix, classes) #getdata accessor getdata(prj) #getdata accessor specific getdata(prj, "line") #plot the result (if dim >2, then plot in 3d) plot(prj) #plot the result (if dim=2, then plot in 2d) prj2 <- pcp(pcpmatrix[,1:2], classes) plot(prj2) pcpmatrix Simulated data used to demonstrate the Pcp method. Pcp demonstration matrix. Usage pcpmatrix

PermutationResults-class 9 Format Matrix rownames Groups colnames dimension number Value simulated matrix Examples pcpmatrix PermutationResults-class Permutation test Usage Test how the classification performs compared to random (eg. permuted) data. ## S4 method for signature 'PermutationResults' getdata(x, n = NULL) ## S4 method for signature 'PermutationResults' c(x,..., recursive = FALSE) pvalue(x,...) ## S4 method for signature 'PermutationResults' pvalue(x,...) conf.int(x,...) ## S4 method for signature 'PermutationResults' conf.int(x, conf.level = 0.99,...) ## S4 method for signature 'PermutationResults' initialize(.object,..., scores.real, scores.vec) permute(mat,...) ## S4 method for signature 'matrix' permute(mat, classes, projmethod = "pcp", iter = 100, user.permutations = NULL, seed = 3, df = NULL, verbose = TRUE,...) ## S4 method for signature 'PermutationResults,missing'

10 PermutationResults-class plot(x, y, comparison = "all",...) ## S4 method for signature 'PermutationResults' show(object) Arguments x n matrix for the function permute, otherwise it is a PermutationResults object data to extract from ClassifiedPoints (NULL gives all)... arguments to pass on recursive conf.level.object scores.real scores.vec mat classes projmethod iter dont use (belongs to default generic of combine c() ) confidence level for the returned confidence interval internal object the real score all permuted scores matrix with samples on rows, PCs in columns. Ordered PCs, with PC1 to the left. vector in same order as rows in matrix pcp or mlp integer number of iterations to be performed. user.permutations user defined permutation matrix seed df verbose y comparison object random seed to be used by the internal permutation degrees of freedom, passed to smooth.spline makes function more talkative default plot param, which should be set to NULL Specify a comparison i.e. ("grp1 vs grp2") and plot only that comparison. ClassifiedPoints Object Details This is a test suit and will return a summarized object. The default of the parameter iter is set quite low, and in principle the more iterations the better, or until the pvalue converges to a specifc value. If no pre-permuted data has been supplied by the user, then the internal permutation method will perform a sampling without replacement within each dimension. Value The permute function returns an object of class PermutationResults Author(s) Jesper R. Gadin and Jason T. Serviss

PermutationResults-class 11 Examples #use pcp method data(pcpmatrix) classes <- rownames(pcpmatrix) #run function iterations <- 10 pe <- permute( mat=pcpmatrix, classes=classes, iter=iterations, projmethod="pcp" ) #use mlp method data(mlpmatrix) classes <- rownames(mlpmatrix) pe <- permute( mat=mlpmatrix, classes=classes, iter=iterations, projmethod="mlp" ) #getdata accessor getdata(pe) #getdata accessor specific getdata(pe, "scores.vec") #get pvalue pvalue(pe) #plot result plot(pe) #combine three (parallell) jobs on the same matrix pe2 <- c(pe, pe, pe)

Index Topic classification ClassifiedPoints-class, 3 Topic package ClusterSignificance-package, 2 Topic permutation PermutationResults-class, 9 Topic projection Mlp-class, 4 Pcp-class, 7.ClassifiedPoints.Mlp (Mlp-class), 4.Pcp (Pcp-class), 7.PermutationResults c,permutationresults-method ClassifiedPoints ClassifiedPoints-class, 3 classify classify,mlp-method classify,pcp-method ClusterSignificance (ClusterSignificance-package), 2 ClusterSignificance-package, 2 conf.int conf.int,permutationresults-method getdata (Pcp-class), 7 getdata,classifiedpoints-method getdata,mlp-method (Mlp-class), 4 getdata,pcp-method (Pcp-class), 7 getdata,permutationresults-method initialize,mlp-method (Mlp-class), 4 initialize,pcp-method (Pcp-class), 7 initialize,permutationresults-method Mlp (Mlp-class), 4 mlp (Mlp-class), 4 mlp,matrix-method (Mlp-class), 4 Mlp-class, 4 mlpmatrix, 6 Pcp (Pcp-class), 7 pcp (Pcp-class), 7 pcp,matrix-method (Pcp-class), 7 Pcp-class, 7 pcpmatrix, 8 PermutationResults-class, 9 permute permute,matrix-method plot,classifiedpoints,missing-method plot,mlp,missing-method (Mlp-class), 4 plot,pcp,missing-method (Pcp-class), 7 plot,permutationresults,missing-method pvalue pvalue,permutationresults-method show,classifiedpoints-method show,mlp-method (Mlp-class), 4 show,pcp-method (Pcp-class), 7 show,permutationresults-method initialize,classifiedpoints-method 12