Last data update: 2014.03.03

R: PAM50 S4 implementation in R
PAM50-classR Documentation

PAM50 S4 implementation in R

Description

This is a concrete MolecularPermutationClassifier based on Perou et al. (2000 & 2010) PAM50 molecular signature, using genefu package implementation (Haibe-Kains et al. 2014).

Slots

parameters

named list with at least the following fields:

$nPerm

integer with number of permutations. Default: 1e4L

$where

character with significant value used. Default value is "fdr".

$pCutoff

numeric with p-value or fdr cutoff used, i.e., variable<pCutoff. Default: 0.01

$keep

should null distribution simulation values be kept?. Default: FALSE

corCutoff

PAM50 additional numeric parameter with the correlation difference between classes cutoff used, i.e., |ρ(profile,class_A)-ρ(profile,classB)|>corCutoff

exprs

matrix with gene exprs profile, where genes are in rows and subjects as columns, a.k.a., M matrix.

annotation

data.frame with individual annotations (genes, etc). Minimal compulsory fields are:

$probe

same characters as in row.names(M).

$EntrezGene.ID

integer with NCBI Entrez Data Base.

$NCBI.gene.symbol

character with gene mnemonic, a.k.a. gene symbol.

targets

data.frame with additional subject data (optional).

classification

named list with at least the following fields:

$subtype

factor with PAM50 subtype of each sample.

$probability

matrix with the subtype probability of each subtype per sample, as in genefu library.

$correlation

matrix with the observed correlation of each subtype per sample.

permutation

named list with at least the following fields:

$correlation

Only if keep==TRUE is a list of the five subtypes containing a matrix with the permuted null distribution correlations.

$pvalues

matrix with the subject's p-values of the permutation test per subject.

$fdr

matrix with the corresponding adjusted p-values.

$subtype

data.frame where each subject has the reported "PAM50" subtype, the "Permuted" test result i.e. "Assigned", "Not Assigned" or "Ambiguous"; "Classes" whether is a single PAM50 subtype or more than one if Ambiguous case; "Class" if it is needed to assign just one i.e., a single PAM50 subtype or Not Assigned.

Superclassses

Direct descendant from MolecularPermutationClassifier-class.

Subclasses

None declared.

Function

Redefinition from MolecularPermutationClassifier: filtrate, classify, permutate, subjectReporta and databaseReport.

Author(s)

Cristobal Fresno cfresno@bdmg.com.ar, German A. Gonzalez ggonzalez@bdmg.com.ar, Andrea S. Llera allera@leloir.org.ar and Elmer Andres Fernandez efernandez@bdmg.com.ar

References

  1. Haibe-Kains B, Schroeder M, Bontempi G, Sotiriou C and Quackenbush J, 2014, genefu: Relevant Functions for Gene Expression Analysis, Especially in Breast Cancer. R package version 1.16.0, www.pmgenomics.ca/bhklab/

  2. Perou CM, Sorlie T, Eisen MB, et al., 2000, Molecular portraits of human breast tumors. Nature 406:747-752.

  3. Perou CM, Parker JS, Prat A, Ellis MJ, Bernard PB., 2010, Clinical implementation of the intrinsic subtypes of breast cancer, The Lancet Oncology 11(8):718-719

See Also

Other MolecularPermutationClassifier PAM50: filtrate, loadBCDataset

Examples

##Example 1: Create a PAM50 object -----------------------------------------  
##1) Just an empty object
object<-PAM50()
object

##2) Using Breast Cancer NKI database, if available. 
if(requireNamespace("breastCancerNKI")){
    object<-loadBCDataset(Class=PAM50, libname="nki", verbose=TRUE)  
    object    
    ##Now we can inspect the object   
    head(exprs(object))      ##The gene expression    
    head(annotation(object)) ##The available annotation 
    head(targets(object))    ##The clinical data present in the package  
}

##Example 2: Build a PAM50 object with user data -------------------------   
##Option 1: using PAM50 constructor. The user will only need:   
##a) The M gene expression object, i. e., gene in rows and sample in columns  
##b) The annotation data.frame which must include the compulsory fields   
## "probe", "NCBI.gene.symbol" and "EntrezGene.ID"
M<-pam50$centroids
genes<-pam50$centroids.map
names(genes)<-c("probe", "NCBI.gene.symbol", "EntrezGene.ID")  
object<-PAM50(exprs=M, annotation=genes)   
object

##Option 2: Two ways to build it from a MAList (as or as.PAM50)-------------
##Let's use PAM50 classifier's centroids toy example, i. e., the five subject 
##subtypes, which must correctly classify all the subject. 
M<-pam50$centroids
genes<-pam50$centroids.map
names(genes)<-c("probe", "NCBI.gene.symbol", "EntrezGene.ID")  
maux<-new("MAList", list(M=M, genes=genes))  
##calling as function  
object<-as(maux, "PAM50")   
object
##same result with as.PAM50 function
object<-as.PAM50(maux)
object

##Example3: Work with PAM50 object: filtrate, classify and permutate--------
##1)Keep only annotated genes presentes in PAM50 centroids 
object<-filtrate(object, verbose=TRUE)   

##2)Get PAM50 subtypes without any normalization   
object<-classify(object, std="none", verbose=TRUE)  
##Now we can inspect the how the calssification went
head(classification(object))

##3)Obtain the permutation subtype 
##Let's run a quick example with 100 permutations. It is recommended at 
##least 10.000   
object<-permutate(object, nPerm=100, pCutoff=0.01, corCutoff=0.1, 
    keep=TRUE, seed=1234567890, verbose=TRUE)  
object
##Now we can inspect the how the permutation went
head(permutation(object))
##Which parameters were used? 
parameters(object)

##Example 4: Obtain summary statistics and reports--------------------------  
##1) Let's check if we have a diagonal contigency matrix, i. e., no mistake   
##is made in subtype assesment.
summary(object)

##2)Let's take a look at the how the patient genes behave according 
## to PAM50  
subjectReport(object, subject=1)   
##3)Just get a pdf with all the used subjects (PAM50 centroids in this    
##example).
#databaseReport(object, fileName="PAM50.pdf", verbose=TRUE)  

Results


R version 3.3.1 (2016-06-21) -- "Bug in Your Hair"
Copyright (C) 2016 The R Foundation for Statistical Computing
Platform: x86_64-pc-linux-gnu (64-bit)

R is free software and comes with ABSOLUTELY NO WARRANTY.
You are welcome to redistribute it under certain conditions.
Type 'license()' or 'licence()' for distribution details.

R is a collaborative project with many contributors.
Type 'contributors()' for more information and
'citation()' on how to cite R or R packages in publications.

Type 'demo()' for some demos, 'help()' for on-line help, or
'help.start()' for an HTML browser interface to help.
Type 'q()' to quit R.

> library(pbcmc)
Loading required package: genefu
Loading required package: survcomp
Loading required package: survival
Loading required package: prodlim
Loading required package: mclust
Package 'mclust' version 5.2
Type 'citation("mclust")' for citing this R package in publications.
Loading required package: limma
Loading required package: biomaRt
Loading required package: iC10
Loading required package: pamr
Loading required package: cluster
Loading required package: iC10TrainingData
Loading required package: AIMS
Loading required package: e1071
Loading required package: Biobase
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:limma':

    plotMA

The following objects are masked from 'package:stats':

    IQR, mad, xtabs

The following objects are masked from 'package:base':

    Filter, Find, Map, Position, Reduce, anyDuplicated, append,
    as.data.frame, cbind, colnames, do.call, duplicated, eval, evalq,
    get, grep, grepl, intersect, is.unsorted, lapply, lengths, mapply,
    match, mget, order, paste, pmax, pmax.int, pmin, pmin.int, rank,
    rbind, rownames, sapply, setdiff, sort, table, tapply, union,
    unique, unsplit

Welcome to Bioconductor

    Vignettes contain introductory material; view with
    'browseVignettes()'. To cite Bioconductor, see
    'citation("Biobase")', and for packages 'citation("pkgname")'.

No methods found in "BiocGenerics" for requests: unlist
> png(filename="/home/ddbj/snapshot/RGM3/R_BC/result/pbcmc/PAM50-class.Rd_%03d_medium.png", width=480, height=480)
> ### Name: PAM50-class
> ### Title: PAM50 S4 implementation in R
> ### Aliases: PAM50 PAM50-class
> 
> ### ** Examples
> 
> ##Example 1: Create a PAM50 object -----------------------------------------  
> ##1) Just an empty object
> object<-PAM50()
> object
An empty PAM50 molecular permutation classifier object
> 
> ##2) Using Breast Cancer NKI database, if available. 
> if(requireNamespace("breastCancerNKI")){
+     object<-loadBCDataset(Class=PAM50, libname="nki", verbose=TRUE)  
+     object    
+     ##Now we can inspect the object   
+     head(exprs(object))      ##The gene expression    
+     head(annotation(object)) ##The available annotation 
+     head(targets(object))    ##The clinical data present in the package  
+ }
Loading required namespace: breastCancerNKI
Loading dataset...
Building a PAM50 object
       samplename dataset series id filename size age er grade pgr her2
NKI_4       NKI_4     NKI    NKI  4       NA  2.0  41  1     3  NA   NA
NKI_6       NKI_6     NKI    NKI  6       NA  1.3  49  1     2  NA   NA
NKI_7       NKI_7     NKI    NKI  7       NA  2.0  46  0     1  NA   NA
NKI_8       NKI_8     NKI    NKI  8       NA  2.8  48  0     3  NA   NA
NKI_9       NKI_9     NKI    NKI  9       NA  1.5  48  1     3  NA   NA
NKI_11     NKI_11     NKI    NKI 11       NA  2.2  37  1     3  NA   NA
       brca.mutation e.dmfs t.dmfs node t.rfs e.rfs treatment tissue t.os e.os
NKI_4              0      0   4747    0  4747     0         0      1 4744    0
NKI_6              0      0   4075    0  4075     0         0      1 4072    0
NKI_7              0      0   3703    0  3703     0         0      1 3700    0
NKI_8              0      0   3215    0  3215     0         0      1 3213    0
NKI_9              0      0   3760    0  3760     0         0      1 3757    0
NKI_11             0      0   2120    0  2120     0         0      1 2119    0
> 
> ##Example 2: Build a PAM50 object with user data -------------------------   
> ##Option 1: using PAM50 constructor. The user will only need:   
> ##a) The M gene expression object, i. e., gene in rows and sample in columns  
> ##b) The annotation data.frame which must include the compulsory fields   
> ## "probe", "NCBI.gene.symbol" and "EntrezGene.ID"
> M<-pam50$centroids
> genes<-pam50$centroids.map
> names(genes)<-c("probe", "NCBI.gene.symbol", "EntrezGene.ID")  
> object<-PAM50(exprs=M, annotation=genes)   
> object
A PAM50 molecular permutation classifier object
Dimensions:
           nrow ncol
exprs        50    5
annotation   50    3
targets       0    0
> 
> ##Option 2: Two ways to build it from a MAList (as or as.PAM50)-------------
> ##Let's use PAM50 classifier's centroids toy example, i. e., the five subject 
> ##subtypes, which must correctly classify all the subject. 
> M<-pam50$centroids
> genes<-pam50$centroids.map
> names(genes)<-c("probe", "NCBI.gene.symbol", "EntrezGene.ID")  
> maux<-new("MAList", list(M=M, genes=genes))  
> ##calling as function  
> object<-as(maux, "PAM50")   
> object
A PAM50 molecular permutation classifier object
Dimensions:
           nrow ncol
exprs        50    5
annotation   50    3
targets       0    0
> ##same result with as.PAM50 function
> object<-as.PAM50(maux)
> object
A PAM50 molecular permutation classifier object
Dimensions:
           nrow ncol
exprs        50    5
annotation   50    3
targets       0    0
> 
> ##Example3: Work with PAM50 object: filtrate, classify and permutate--------
> ##1)Keep only annotated genes presentes in PAM50 centroids 
> object<-filtrate(object, verbose=TRUE)   
Keeping only annotated EntrezGene.ID genes
Keeping only PAM50 available genes.
> 
> ##2)Get PAM50 subtypes without any normalization   
> object<-classify(object, std="none", verbose=TRUE)  
Getting PAM50 subtypes...
50/50 probes are used for clustering
no standardization of the gene expressions
> ##Now we can inspect the how the calssification went
> head(classification(object))
$subtype
 Basal   Her2   LumA   LumB Normal 
 Basal   Her2   LumA   LumB Normal 
Levels: Basal Her2 LumA LumB Normal

$probability
            Basal      Her2      LumA      LumB    Normal
Basal  0.89431418 0.0000000 0.0000000 0.0000000 0.1056858
Her2   0.00000000 0.6822947 0.0000000 0.3177053 0.0000000
LumA   0.00000000 0.0000000 0.6823842 0.0000000 0.3176158
LumB   0.00000000 0.3177053 0.0000000 0.6822947 0.0000000
Normal 0.07462325 0.0000000 0.2939143 0.0000000 0.6314624

$correlation
            Basal       Her2       LumA       LumB     Normal
Basal   1.0000000 -0.1461224 -0.6492677 -0.3604802  0.1181753
Her2   -0.1461224  1.0000000 -0.3813205  0.4656423 -0.6217047
LumA   -0.6492677 -0.3813205  1.0000000 -0.2027851  0.4654502
LumB   -0.3604802  0.4656423 -0.2027851  1.0000000 -0.7635534
Normal  0.1181753 -0.6217047  0.4654502 -0.7635534  1.0000000

> 
> ##3)Obtain the permutation subtype 
> ##Let's run a quick example with 100 permutations. It is recommended at 
> ##least 10.000   
> object<-permutate(object, nPerm=100, pCutoff=0.01, corCutoff=0.1, 
+     keep=TRUE, seed=1234567890, verbose=TRUE)  
Obtaining 100 permutations for 5 subjects...
   |                                                                               |                                                                      |   0%   |                                                                               |===================================                                   |  50%   |                                                                               |======================================================================| 100%

Obtaining 100 permutations for 5 subjects... done.
> object
A PAM50 molecular permutation classifier object
Dimensions:
           nrow ncol
exprs        50    5
annotation   50    3
targets       0    0
Classification: 
            nrow ncol
probability    5    5
correlation    5    5
$subtype

 Basal   Her2   LumA   LumB Normal 
     1      1      1      1      1 

Permutations test ran with following parameters:
 Permutations=100, fdr<0.01, corCutoff>0.1, keep=TRUE
Permutation: 
correlation available: TRUE 
        nrow ncol
pvalues    5    5
fdr        5    5
subtype    5    5
> ##Now we can inspect the how the permutation went
> head(permutation(object))
$correlation
$correlation$Basal
              Basal         Her2         LumA          LumB        Normal
  [1,]  0.039711885  0.347899160 -0.106458583  0.0906122449 -0.1870348139
  [2,] -0.122112845  0.107899160  0.099927971  0.1094357743 -0.0867707083
  [3,] -0.029531813 -0.114717887  0.105114046 -0.0657382953 -0.0106122449
  [4,] -0.011764706  0.027803121  0.089651861 -0.0324129652  0.0363505402
  [5,]  0.092629052 -0.075918367 -0.120000000 -0.1611044418  0.0162785114
  [6,] -0.161584634  0.125474190 -0.059879952  0.0838895558 -0.0965666267
  [7,] -0.263961585  0.128163265  0.223049220  0.0153181273 -0.0582472989
  [8,]  0.007442977 -0.087827131  0.214789916 -0.3078511405  0.2533973589
  [9,]  0.190012005  0.083313325 -0.214117647  0.0091716687 -0.1888595438
 [10,] -0.097142857 -0.100024010  0.209411765 -0.1054021609  0.3054501801
 [11,]  0.260888355 -0.191164466 -0.057767107 -0.2033613445  0.1086674670
 [12,]  0.187322929  0.053541417 -0.175990396 -0.0790876351 -0.1024249700
 [13,]  0.024633854 -0.081584634 -0.012148860 -0.1825210084  0.1016566627
 [14,] -0.077743097  0.099639856 -0.108667467  0.2038415366 -0.1608163265
 [15,]  0.150540216 -0.057671068 -0.137671068  0.1780072029 -0.0439375750
 [16,]  0.084369748 -0.194141657  0.154669868 -0.1667707083  0.3276350540
 [17,]  0.078415366 -0.124225690 -0.046626651  0.1060744298 -0.0169507803
 [18,] -0.238127251 -0.150732293  0.219687875  0.1546698679  0.0548859544
 [19,]  0.147563025 -0.013397359 -0.098391357  0.0271308523 -0.0121488595
 [20,]  0.095798319  0.193853541 -0.202496999  0.3390636255 -0.2263145258
 [21,] -0.234093637 -0.170900360  0.343865546  0.0370228091  0.1085714286
 [22,] -0.134213685  0.062665066 -0.058823529  0.1488115246 -0.1345978391
 [23,] -0.114813926  0.043841537  0.116254502  0.0050420168  0.1946218487
 [24,] -0.063433373  0.078895558  0.148427371 -0.1059783914  0.0285714286
 [25,] -0.127202881 -0.287683073  0.141992797 -0.1140456182  0.1955822329
 [26,]  0.140456182  0.031836735 -0.195582233  0.0547899160 -0.1621608643
 [27,]  0.055366146 -0.241104442  0.139399760 -0.2454261705  0.2557022809
 [28,]  0.008883553 -0.139399760  0.073037215  0.0276110444  0.0531572629
 [29,] -0.046338535  0.157358944 -0.057959184 -0.0253061224 -0.1964465786
 [30,]  0.063337335  0.225450180 -0.145066026  0.0703481393  0.0035054022
 [31,]  0.120960384 -0.102809124  0.127683073 -0.1796398559  0.2818247299
 [32,] -0.027034814  0.113565426  0.002833133  0.2637695078 -0.2142136855
 [33,]  0.002929172  0.032412965 -0.212677071  0.0535414166 -0.2205522209
 [34,]  0.112797119  0.205186074 -0.173973589 -0.1118367347  0.0084993998
 [35,] -0.075630252  0.253589436 -0.241584634  0.1447779112 -0.2112364946
 [36,]  0.238799520  0.075822329 -0.252436975 -0.1306602641 -0.1074189676
 [37,] -0.059975990 -0.054885954  0.187226891 -0.0622809124  0.1638895558
 [38,]  0.020696279  0.259255702 -0.078703481  0.2237214886 -0.1361344538
 [39,] -0.207779112  0.075342137  0.089555822  0.1870348139 -0.1147178872
 [40,]  0.070252101 -0.033565426  0.053733493 -0.1203841537  0.0729411765
 [41,] -0.022040816 -0.124417767  0.047394958 -0.0434573830 -0.0344297719
 [42,] -0.272412965 -0.049795918  0.243697479 -0.1037695078  0.1068427371
 [43,]  0.204609844  0.240240096 -0.314861945  0.0616086435 -0.2048019208
 [44,]  0.082833133 -0.035006002  0.033661465  0.0381752701  0.0028331333
 [45,] -0.035390156 -0.160816327  0.082929172 -0.1272989196  0.1029051621
 [46,] -0.059495798  0.036542617  0.037214886  0.1032893157 -0.1221128451
 [47,] -0.118751501 -0.094645858  0.131044418  0.0277070828  0.0676590636
 [48,]  0.202593037 -0.144297719 -0.167827131  0.0384633854  0.0051380552
 [49,] -0.067370948 -0.045666267  0.082545018  0.0771668667  0.0206962785
 [50,] -0.073709484 -0.089267707 -0.018295318  0.1628331333 -0.0470108043
 [51,]  0.171188475 -0.086290516 -0.031164466 -0.1859783914  0.1212484994
 [52,]  0.002545018 -0.109627851  0.017334934 -0.1863625450  0.1510204082
 [53,]  0.216134454  0.361536615 -0.545546218  0.3916926771 -0.4788955582
 [54,] -0.051044418  0.159183673  0.012821128 -0.0483553421  0.1826170468
 [55,]  0.169651861  0.043361345 -0.089267707 -0.0629531813  0.1284513806
 [56,]  0.008979592  0.043937575  0.005234094  0.0206962785 -0.0742857143
 [57,] -0.014741897 -0.081776711  0.155630252 -0.0920528211  0.1053061224
 [58,] -0.234957983 -0.022521008  0.227082833  0.1932773109 -0.0089795918
 [59,] -0.091668667  0.037022809  0.070924370  0.1644657863 -0.1444897959
 [60,] -0.071212485 -0.196446579  0.114813926 -0.0889795918  0.0754381753
 [61,]  0.354813926  0.016278511 -0.286146459 -0.1938535414  0.0782232893
 [62,]  0.088115246 -0.126914766  0.105210084 -0.2723169268  0.1926050420
 [63,]  0.180312125 -0.004945978 -0.127490996 -0.1217286915 -0.0227130852
 [64,] -0.011092437 -0.008787515 -0.126626651  0.0718847539 -0.1648499400
 [65,]  0.229099640 -0.245810324 -0.172629052 -0.0846578631  0.0323169268
 [66,]  0.132677071 -0.006674670 -0.022136855 -0.1774309724  0.1662905162
 [67,] -0.052292917  0.031452581  0.003985594 -0.1470828331  0.0359663866
 [68,]  0.127106843  0.141128451 -0.278655462  0.1184633854 -0.1883793517
 [69,] -0.096662665  0.190204082 -0.056230492  0.2154621849 -0.3564465786
 [70,]  0.152749100  0.064105642 -0.094165666  0.0004321729 -0.1159663866
 [71,]  0.069099640 -0.034141657  0.005618247 -0.1257623049  0.1274909964
 [72,]  0.073517407 -0.228907563  0.128547419 -0.0114765906  0.2043217287
 [73,]  0.188283313  0.099831933 -0.005426170 -0.1699399760  0.0948379352
 [74,] -0.170228091  0.061128451 -0.019447779  0.3787274910 -0.2952701080
 [75,]  0.218631453  0.081104442  0.016278511 -0.1731092437  0.1685954382
 [76,]  0.198271309 -0.187707083 -0.099159664  0.0254981993 -0.0085954382
 [77,] -0.058823529  0.082160864  0.047490996 -0.0343337335  0.0744777911
 [78,]  0.375558223  0.078319328 -0.204129652 -0.1072268908 -0.0093637455
 [79,]  0.063625450 -0.221800720  0.022905162 -0.2152701080  0.2437935174
 [80,] -0.067082833  0.017334934  0.002064826  0.0449939976  0.1128931573
 [81,]  0.149483794 -0.432989196  0.157647059 -0.2848019208  0.2682833133
 [82,]  0.033565426  0.192989196 -0.231212485  0.0853301321 -0.1285474190
 [83,]  0.266458583  0.086962785 -0.052196879  0.0812004802 -0.0317406963
 [84,]  0.123169268  0.088211285 -0.091092437 -0.0809123649 -0.0947418968
 [85,] -0.102424970 -0.078031212  0.201056423 -0.0072509004  0.1122208884
 [86,]  0.114141657 -0.035006002 -0.046626651  0.0176230492  0.0742857143
 [87,] -0.019351741  0.090612245 -0.013685474 -0.0337575030 -0.0258823529
 [88,] -0.308043217  0.172244898  0.172629052  0.1336374550  0.0334693878
 [89,]  0.187899160 -0.021368547 -0.148715486 -0.0903241297 -0.0193517407
 [90,] -0.100216086 -0.021752701  0.223913565 -0.1023289316  0.2456182473
 [91,] -0.092917167  0.111452581  0.037214886 -0.1436254502  0.1254741897
 [92,] -0.374213685  0.116254502  0.254645858  0.3475150060 -0.1560144058
 [93,]  0.097623049 -0.065834334 -0.144201681  0.0477791116 -0.0331812725
 [94,]  0.154093637  0.189723890 -0.348571429  0.3002641056 -0.2498439376
 [95,]  0.009651861 -0.026938776 -0.095030012 -0.1602400960 -0.0008163265
 [96,]  0.136710684 -0.142376951 -0.037503001 -0.1044417767  0.1931812725
 [97,] -0.206338535  0.188955582  0.057190876  0.1971188475 -0.2681872749
 [98,]  0.114045618 -0.169363745 -0.178583433  0.1189435774 -0.1206722689
 [99,]  0.134981993 -0.054693878 -0.089171669 -0.0870588235  0.0060984394
[100,] -0.389003601 -0.077166867  0.282112845  0.1367106843 -0.1255702281

$correlation$Her2
               Basal          Her2         LumA         LumB        Normal
  [1,]  1.160624e-01 -0.3245618247  0.055078031 -0.202593037  0.2888355342
  [2,]  7.841537e-02  0.1026170468 -0.149195678  0.150444178 -0.2878751501
  [3,]  3.222089e-02 -0.1512124850  0.235630252 -0.271452581  0.2525330132
  [4,] -2.100840e-01  0.1865546218 -0.116542617  0.260120048 -0.3060264106
  [5,]  1.234094e-02  0.0488355342 -0.011860744 -0.109339736  0.0294357743
  [6,] -6.506603e-02  0.0397118848  0.006290516  0.169555822 -0.1799279712
  [7,]  2.234334e-01 -0.2337094838 -0.034045618 -0.127298920  0.0479711885
  [8,] -4.801921e-05 -0.4123409364  0.076398559 -0.051908764  0.1850180072
  [9,] -6.996399e-02  0.0084033613  0.059207683  0.198463385 -0.1100120048
 [10,] -1.232653e-01 -0.1134693878  0.228811525 -0.132196879  0.1703241297
 [11,] -1.921248e-01 -0.0367346939  0.276926771 -0.012917167  0.1141416567
 [12,] -9.843938e-03 -0.0964705882  0.136998800 -0.124705882  0.0475870348
 [13,]  2.256903e-03  0.1712845138 -0.134309724  0.153805522  0.0007202881
 [14,] -1.280672e-01  0.1292196879  0.196638655  0.085138055 -0.0644897959
 [15,]  1.069388e-01  0.1206722689 -0.279903962  0.202112845 -0.2018247299
 [16,]  6.343337e-02 -0.0714045618 -0.010228091 -0.146506603  0.1733973589
 [17,] -2.091236e-01  0.0820648259  0.077935174  0.103193277 -0.0596878752
 [18,] -4.883553e-02 -0.1153901561  0.154573830 -0.209891957  0.2383193277
 [19,]  9.378151e-02  0.1097238896 -0.071980792 -0.041248499  0.0006242497
 [20,]  3.731092e-02  0.0538295318 -0.053061224  0.120192077 -0.0556542617
 [21,]  9.301321e-02 -0.1008883553 -0.010420168 -0.156782713  0.1908763505
 [22,]  2.857143e-02  0.0133013205  0.024345738  0.024153661  0.1054981993
 [23,] -3.422329e-01  0.0827370948  0.212677071 -0.020408163  0.0088835534
 [24,] -5.997599e-02 -0.2847058824  0.141320528 -0.018871549  0.1178871549
 [25,] -2.446579e-01 -0.0606482593  0.056998800  0.221224490 -0.0565186074
 [26,] -9.651861e-03  0.1524609844 -0.139783914 -0.071116447 -0.1115486194
 [27,]  1.381513e-01 -0.0592076831 -0.097719088  0.020696279 -0.0212725090
 [28,]  1.587035e-01  0.1224969988 -0.194429772  0.059111645 -0.1248019208
 [29,] -6.372149e-02 -0.0574789916  0.054213685  0.219687875 -0.1158703481
 [30,]  1.848259e-01  0.0197358944 -0.211236495 -0.065354142  0.0448979592
 [31,] -2.433133e-01  0.2230492197 -0.061416567  0.218727491 -0.1481392557
 [32,]  2.530132e-01  0.2313085234 -0.321488595 -0.006194478 -0.0884993998
 [33,]  2.732293e-02  0.1478511405 -0.034429772 -0.105306122 -0.0359663866
 [34,]  3.606242e-02  0.0641056423 -0.062953181 -0.183961585 -0.0953181273
 [35,] -9.733493e-02  0.0532533013 -0.036158463  0.290852341 -0.2085474190
 [36,]  1.709004e-01  0.1459303721 -0.159471789  0.054693878 -0.1536134454
 [37,]  2.178631e-01  0.0263625450 -0.144297719 -0.024537815 -0.1149099640
 [38,] -1.175990e-01  0.0760144058 -0.003409364  0.165618247 -0.0839855942
 [39,] -2.456182e-01  0.2638655462  0.047010804  0.159375750 -0.1158703481
 [40,]  1.616807e-01  0.1471788715 -0.246962785 -0.019447779  0.0130132053
 [41,]  1.815606e-01 -0.1597599040  0.022713085 -0.134885954  0.1100120048
 [42,] -1.484274e-01 -0.0844657863  0.056614646 -0.008019208  0.0659303721
 [43,]  7.927971e-02  0.1501560624 -0.207587035  0.365762305 -0.3842977191
 [44,] -1.339256e-01 -0.3837214886  0.225258103  0.118847539  0.1077070828
 [45,]  1.289316e-01 -0.1023289316 -0.007346939 -0.042689076  0.1669627851
 [46,] -1.560144e-01 -0.0740936375  0.247346939 -0.127683073  0.2313085234
 [47,] -7.438175e-02  0.0675630252 -0.018967587  0.200672269 -0.1491956783
 [48,] -1.702281e-01  0.1429531813 -0.035582233  0.072941176 -0.0444177671
 [49,] -3.990396e-02  0.3689315726 -0.142569028  0.260504202 -0.3053541417
 [50,]  5.978391e-02  0.1313325330 -0.312268908  0.025402161 -0.0601680672
 [51,]  5.613445e-02  0.1572629052 -0.016566627 -0.111260504  0.0837935174
 [52,] -3.394958e-02  0.0521008403 -0.012917167  0.005426170 -0.0934933974
 [53,] -6.381753e-02  0.0031212485  0.167154862 -0.038463385  0.0934933974
 [54,]  1.636014e-01 -0.0880192077 -0.199615846 -0.100408163  0.0416326531
 [55,]  3.577431e-02 -0.2490756303  0.071980792 -0.243793517  0.1934693878
 [56,]  2.064826e-03 -0.1030012005  0.043457383 -0.222665066  0.2557983193
 [57,]  8.561825e-02  0.0519087635 -0.202112845  0.094837935 -0.1813685474
 [58,]  3.030012e-02 -0.0860984394  0.092436975 -0.123649460  0.1608163265
 [59,] -5.959184e-02  0.0001440576  0.033277311  0.001104442  0.1332533013
 [60,]  2.435054e-01 -0.1758943577  0.102617047 -0.333013205  0.2296758703
 [61,]  1.133733e-01 -0.2891236495 -0.089075630 -0.091188475 -0.0416326531
 [62,]  1.191357e-01 -0.0229051621  0.047202881 -0.082352941  0.1066506603
 [63,] -3.942377e-02 -0.1699399760  0.178679472 -0.092821128  0.1736854742
 [64,]  5.248499e-02  0.0030252101  0.064585834 -0.126914766  0.0697719088
 [65,]  1.228812e-01 -0.4438415366  0.079759904 -0.208355342  0.4124369748
 [66,] -1.637455e-02 -0.2356302521  0.004561825 -0.028187275  0.0804321729
 [67,] -8.379352e-02  0.0837935174  0.081680672  0.113277311 -0.1294117647
 [68,] -1.030012e-01 -0.0649699880  0.082833133 -0.048163265  0.1412244898
 [69,] -5.906363e-03 -0.0396158463  0.052100840 -0.009747899  0.0739975990
 [70,]  7.659064e-02  0.2429291717 -0.102617047 -0.015510204 -0.1255702281
 [71,]  4.081633e-03 -0.2910444178  0.082448980  0.188763505  0.0893637455
 [72,]  1.715726e-01  0.2868187275 -0.204225690  0.059303721 -0.2522448980
 [73,]  1.621609e-01  0.0665066026 -0.076878752  0.003025210 -0.0642977191
 [74,] -1.429532e-01 -0.1573589436  0.150348139 -0.114813926  0.3217767107
 [75,] -6.496999e-02 -0.1762785114  0.154669868 -0.286050420  0.2179591837
 [76,]  1.795438e-01 -0.0013925570 -0.184153661 -0.038655462 -0.0130132053
 [77,]  5.906363e-03  0.0461464586  0.074093637 -0.099255702  0.1563025210
 [78,] -2.129652e-01 -0.0014885954  0.084081633  0.270108043 -0.0739015606
 [79,]  2.194478e-02  0.0411524610  0.083601441 -0.133349340  0.0427851140
 [80,]  1.215366e-01 -0.1347899160  0.038655462 -0.058823529  0.0217527011
 [81,] -1.290276e-01 -0.0586314526  0.223817527 -0.006386555  0.1003121248
 [82,]  1.461224e-01 -0.0634333733 -0.135270108 -0.229771909  0.0827370948
 [83,]  1.029052e-01 -0.2702040816  0.049027611 -0.269051621  0.2225690276
 [84,]  9.349340e-02  0.1405522209 -0.072460984 -0.170804322 -0.1344057623
 [85,]  2.129652e-01  0.3248499400 -0.383625450  0.056806723 -0.2775030012
 [86,]  6.602641e-02  0.0634333733 -0.110972389 -0.003985594  0.0297238896
 [87,]  1.732053e-01 -0.0708283313 -0.125954382  0.120768307 -0.0570948379
 [88,]  1.853061e-01  0.1108763505 -0.312845138  0.018007203 -0.1599519808
 [89,] -2.933974e-02 -0.1777190876  0.131908764 -0.128835534  0.2361104442
 [90,] -6.482593e-03  0.0401920768 -0.107034814  0.159951981 -0.1601440576
 [91,]  2.695318e-01  0.0483553421 -0.146314526 -0.107803121 -0.0122448980
 [92,]  2.780312e-02 -0.1093397359 -0.002641056  0.137863145 -0.1672509004
 [93,]  1.599520e-01 -0.3982232893  0.028571429 -0.119615846  0.1800240096
 [94,]  2.256423e-01 -0.1481392557  0.052388956 -0.252821128  0.1790636255
 [95,] -7.678271e-02 -0.0295318127  0.164369748 -0.288163265  0.2419687875
 [96,]  2.424970e-02 -0.0235774310  0.083505402  0.104825930 -0.0759183673
 [97,]  8.388956e-02  0.1234573830 -0.097142857 -0.010324130 -0.0461464586
 [98,]  1.784874e-01 -0.0422088836 -0.032028812  0.025882353  0.1038655462
 [99,]  1.669628e-01  0.2126770708 -0.085426170 -0.001488595 -0.1248019208
[100,]  1.620648e-01 -0.2778871549 -0.043457383 -0.056518607  0.0186794718

$correlation$LumA
              Basal          Her2         LumA         LumB       Normal
  [1,] -0.040192077  0.0466266507  0.126818727 -0.172629052  0.011956783
  [2,] -0.117310924  0.1812725090 -0.188571429  0.164081633 -0.239663866
  [3,] -0.130756303  0.3233133253 -0.132677071  0.268955582 -0.286914766
  [4,]  0.164945978 -0.0573829532  0.064201681 -0.290180072  0.341848739
  [5,] -0.000240096 -0.2612725090  0.120480192 -0.056230492  0.099543818
  [6,]  0.075918367 -0.1997118848  0.176662665 -0.312076831  0.178103241
  [7,]  0.239855942 -0.1088595438  0.043169268 -0.238223289  0.088691477
  [8,]  0.032701080 -0.0073469388 -0.203937575  0.013877551 -0.091572629
  [9,]  0.112316927  0.0007202881  0.029147659 -0.143145258  0.005618247
 [10,] -0.132965186 -0.0522929172  0.169555822  0.165618247 -0.186170468
 [11,]  0.040192077 -0.0299159664 -0.003889556 -0.035774310  0.103865546
 [12,]  0.161104442  0.0209843938 -0.255798319  0.090324130 -0.081872749
 [13,] -0.072749100 -0.0681392557  0.017911164  0.018871549  0.123649460
 [14,] -0.032509004  0.2538775510 -0.136998800  0.125762305 -0.231212485
 [15,]  0.111260504 -0.0299159664 -0.008499400 -0.065738295  0.029147659
 [16,] -0.153997599  0.1448739496  0.049411765  0.202112845 -0.157454982
 [17,] -0.203649460  0.0530612245  0.216614646  0.051140456  0.121536615
 [18,] -0.042304922  0.0122448980  0.093685474  0.025786315  0.001008403
 [19,] -0.119135654 -0.0762064826  0.066794718  0.071692677 -0.057959184
 [20,]  0.176854742 -0.1090516206 -0.054213685 -0.075822329 -0.054213685
 [21,] -0.175318127  0.1168307323 -0.062280912  0.163601441 -0.250036014
 [22,]  0.026170468 -0.2504201681 -0.015510204  0.020312125  0.113565426
 [23,] -0.088595438  0.0909003601  0.096662665 -0.101464586  0.065834334
 [24,]  0.026938776 -0.0110924370 -0.024441777 -0.085138055  0.051332533
 [25,] -0.066314526  0.1579351741 -0.035486194 -0.018391357  0.042304922
 [26,] -0.078511405  0.0672749100 -0.008595438  0.216614646 -0.259735894
 [27,] -0.099543818 -0.0299159664  0.011668667  0.088787515  0.081392557
 [28,]  0.105594238  0.0472989196 -0.006386555 -0.018871549  0.084177671
 [29,] -0.044417767 -0.0667947179  0.166002401 -0.080240096  0.094069628
 [30,] -0.006578631  0.1578391357 -0.126722689 -0.054981993 -0.173493397
 [31,] -0.071596639 -0.0035054022  0.081872749  0.007923169  0.092629052
 [32,] -0.110204082  0.0526770708 -0.014549820  0.268283313 -0.046530612
 [33,]  0.067082833 -0.0841776711  0.035582233 -0.058631453  0.004465786
 [34,] -0.252244898  0.0394237695  0.084177671  0.270588235 -0.209795918
 [35,]  0.113565426  0.1010804322 -0.064201681  0.064201681 -0.059399760
 [36,] -0.069483794 -0.0743817527  0.123457383  0.024153661 -0.009267707
 [37,]  0.135366146 -0.2307322929 -0.016566627 -0.134021609  0.077454982
 [38,]  0.182809124  0.0906122449 -0.304297719  0.151500600 -0.042977191
 [39,]  0.153421369  0.1679231693 -0.260216086  0.091668667 -0.201728691
 [40,] -0.018583433 -0.1071308523 -0.119423770  0.101944778 -0.072268908
 [41,] -0.229195678 -0.1981752701  0.300648259  0.060840336  0.317647059
 [42,]  0.014933974 -0.0617046819  0.037791116 -0.215750300  0.065162065
 [43,]  0.069867947  0.0057142857 -0.125474190 -0.058247299 -0.019351741
 [44,]  0.088883553 -0.1907803121  0.022328932 -0.052869148  0.074573830
 [45,] -0.080240096 -0.2762545018  0.191164466 -0.257719088  0.278559424
 [46,] -0.170996399  0.2036494598  0.012917167  0.219783914 -0.117983193
 [47,] -0.258199280  0.0913805522  0.390828331 -0.126242497  0.134213685
 [48,] -0.034237695 -0.1234573830  0.226794718 -0.021656663  0.036158463
 [49,]  0.130948379 -0.0133013205 -0.368067227 -0.033853541 -0.108187275
 [50,]  0.079279712  0.0619927971 -0.095990396 -0.061704682  0.013589436
 [51,]  0.165426170 -0.0023529412 -0.103289316  0.204033613 -0.140456182
 [52,]  0.238799520  0.2014405762 -0.300168067 -0.042496999 -0.153613445
 [53,]  0.095990396 -0.2935414166  0.018103241 -0.073709484  0.067755102
 [54,] -0.115870348  0.2493637455  0.019543818  0.114141657 -0.064585834
 [55,] -0.020024010 -0.0821608643  0.036638655  0.084945978 -0.014261705
 [56,] -0.231020408  0.1719567827  0.136806723  0.062088836 -0.119615846
 [57,]  0.124993998 -0.0361584634 -0.034717887 -0.069579832  0.048355342
 [58,] -0.230060024  0.1045378151  0.118079232  0.064201681  0.038655462
 [59,] -0.189531813 -0.0320288115  0.135942377 -0.080528211  0.096086435
 [60,] -0.022328932 -0.1006002401  0.043073229 -0.066026411  0.035006002
 [61,] -0.087635054  0.0841776711  0.108955582  0.185882353 -0.144777911
 [62,] -0.138439376 -0.0863865546  0.123649460  0.069771909  0.037599040
 [63,]  0.048355342  0.0183913565 -0.056230492  0.099351741 -0.029915966
 [64,]  0.185786315 -0.0501800720  0.005426170 -0.243025210  0.071308523
 [65,]  0.108187275  0.0113805522 -0.047394958  0.030876351  0.053541417
 [66,]  0.086098439 -0.1505402161  0.002833133  0.044513806 -0.024153661
 [67,]  0.176950780  0.1393997599 -0.238319328 -0.095990396 -0.083889556
 [68,] -0.041440576 -0.1979831933  0.123937575 -0.059879952  0.063817527
 [69,] -0.133445378  0.0044657863  0.168883553  0.084273709  0.043745498
 [70,] -0.113085234 -0.0391356543  0.382761104 -0.203553421  0.194141657
 [71,]  0.078799520 -0.1086674670 -0.066122449 -0.013973589  0.168499400
 [72,]  0.272509004 -0.1039615846 -0.094741897 -0.190588235  0.229291717
 [73,] -0.102905162 -0.1054981993  0.208931573  0.067178872  0.188571429
 [74,] -0.189723890 -0.0138775510  0.176470588  0.312941176 -0.075822329
 [75,]  0.034429772  0.0070588235 -0.021080432  0.180504202 -0.228811525
 [76,] -0.261272509  0.1393997599  0.036446579  0.275486194 -0.182232893
 [77,] -0.095222089  0.0816806723  0.146218487  0.071500600 -0.089555822
 [78,] -0.070060024  0.0062905162  0.093013205 -0.225642257  0.063433373
 [79,]  0.231308523  0.0253061224 -0.132100840 -0.059015606  0.083217287
 [80,]  0.110876351  0.2065306122 -0.297767107  0.004081633 -0.133733493
 [81,]  0.056902761  0.0954141657 -0.100792317  0.079759904 -0.121152461
 [82,] -0.306410564 -0.0901320528  0.279135654 -0.099543818  0.281824730
 [83,]  0.083601441  0.1050180072 -0.033277311 -0.009747899  0.12