intrinsic.cluster: Function to fit a Single Sample Predictor (SSP) as in Perou,...

Description Usage Arguments Value Author(s) References See Also Examples

Description

This function fits the Single Sample Predictor (SSP) as published in Sorlie et al 2003, Hu et al 2006 and Parker et al 2009. This model is actually a nearest centroid classifier where the centroids representing the breast cancer molecular subtypes are identified through hierarchical clustering using an "intrinsic gene list".

Usage

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intrinsic.cluster(data, annot, do.mapping = FALSE, mapping,
  std = c("none", "scale", "robust"), rescale.q = 0.05, intrinsicg,
  number.cluster = 3, mins = 5, method.cor = c("spearman", "pearson"),
  method.centroids = c("mean", "median", "tukey"), filen, verbose = FALSE)

Arguments

data

Matrix of gene expressions with samples in rows and probes in columns, dimnames being properly defined.

annot

Matrix of annotations with at least one column named "EntrezGene.ID", dimnames being properly defined.

do.mapping

TRUE if the mapping through Entrez Gene ids must be performed (in case of ambiguities, the most variant probe is kept for each gene), FALSE otherwise.

mapping

Matrix with columns "EntrezGene.ID" and "probe" used to force the mapping such that the probes are not selected based on their variance.

std

Standardization of gene expressions: scale for traditional standardization based on mean and standard deviation, robust for standardization based on the 0.025 and 0.975 quantiles, none to keep gene expressions unchanged.

rescale.q

Proportion of expected outliers for (robust) rescaling the gene expressions.

intrinsicg

Intrinsic gene lists. May be specified by the user as a matrix wit hat least 2 columns named probe and EntrezGene.ID for the probe names and the corresponding Entrez Gene ids. The intrinsic gene lists published by Sorlie et al. 2003, Hu et al. 2006 and Parker et al. 2009 are stored in ssp2003, ssp2006 and pam50 respectively.

number.cluster

The number of main clusters to be identified by hierarchical clustering.

mins

The minimum number of samples to be in a main cluster.

method.cor

Correlation coefficient used to identified the nearest centroid. May be spearman or pearson.

method.centroids

LMethod to compute a centroid from gene expressions of a cluster of samples: mean, median or tukey (Tukey's Biweight Robust Mean).

filen

Name of the csv file where the subtype clustering model must be stored.

verbose

TRUE to print informative messages, FALSE otherwise.

Value

model

Single Sample Predictor

subtype

Subtypes identified by the SSP. For published intrinsic gene lists, subtypes can be either "Basal", "Her2", "LumA", "LumB" or "Normal".

subtype.proba

Probabilities to belong to each subtype estimated from the correlations to each centroid.

cor

Correlation coefficient to each centroid.

Author(s)

Benjamin Haibe-Kains

References

T. Sorlie and R. Tibshirani and J. Parker and T. Hastie and J. S. Marron and A. Nobel and S. Deng and H. Johnsen and R. Pesich and S. Geister and J. Demeter and C. Perou and P. E. Lonning and P. O. Brown and A. L. Borresen-Dale and D. Botstein (2003) "Repeated Observation of Breast Tumor Subtypes in Independent Gene Expression Data Sets", Proceedings of the National Academy of Sciences, 1(14):8418–8423

Hu, Zhiyuan and Fan, Cheng and Oh, Daniel and Marron, JS and He, Xiaping and Qaqish, Bahjat and Livasy, Chad and Carey, Lisa and Reynolds, Evangeline and Dressler, Lynn and Nobel, Andrew and Parker, Joel and Ewend, Matthew and Sawyer, Lynda and Wu, Junyuan and Liu, Yudong and Nanda, Rita and Tretiakova, Maria and Orrico, Alejandra and Dreher, Donna and Palazzo, Juan and Perreard, Laurent and Nelson, Edward and Mone, Mary and Hansen, Heidi and Mullins, Michael and Quackenbush, John and Ellis, Matthew and Olopade, Olufunmilayo and Bernard, Philip and Perou, Charles (2006) "The molecular portraits of breast tumors are conserved across microarray platforms", BMC Genomics, 7(96)

Parker, Joel S. and Mullins, Michael and Cheang, Maggie C.U. and Leung, Samuel and Voduc, David and Vickery, Tammi and Davies, Sherri and Fauron, Christiane and He, Xiaping and Hu, Zhiyuan and Quackenbush, John F. and Stijleman, Inge J. and Palazzo, Juan and Marron, J.S. and Nobel, Andrew B. and Mardis, Elaine and Nielsen, Torsten O. and Ellis, Matthew J. and Perou, Charles M. and Bernard, Philip S. (2009) "Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes", Journal of Clinical Oncology, 27(8):1160–1167

See Also

subtype.cluster, intrinsic.cluster.predict, ssp2003, ssp2006, pam50

Examples

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## load SSP signature published in Sorlie et al. 2003
data(ssp2003)
## load NKI data
data(nkis)
## load VDX data
data(vdxs)
ssp2003.nkis <- intrinsic.cluster(data=data.nkis, annot=annot.nkis,
  do.mapping=TRUE, std="robust",
  intrinsicg=ssp2003$centroids.map[ ,c("probe", "EntrezGene.ID")],
  number.cluster=5, mins=5, method.cor="spearman",
  method.centroids="mean", verbose=TRUE)
str(ssp2003.nkis, max.level=1)

Example output

Loading required package: survcomp
Loading required package: survival
Loading required package: prodlim
Loading required package: mclust
Package 'mclust' version 5.3
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, sd, var, xtabs

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

    Filter, Find, Map, Position, Reduce, anyDuplicated, append,
    as.data.frame, cbind, colMeans, colSums, 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, rowMeans, rowSums, rownames, sapply,
    setdiff, sort, table, tapply, union, unique, unsplit, which,
    which.max, which.min

Welcome to Bioconductor

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

76/500 probes are used for clustering
robust standardization of the gene expressions
List of 4
 $ model        :List of 7
 $ subtype      : Named chr [1:150] "cluster.1" "cluster.2" "cluster.1" "cluster.1" ...
  ..- attr(*, "names")= chr [1:150] "NKI_123" "NKI_327" "NKI_291" "NKI_370" ...
 $ subtype.proba: num [1:150, 1:5] 0.435 0.245 0.462 0.504 0.565 ...
  ..- attr(*, "dimnames")=List of 2
 $ cor          : num [1:150, 1:5] 0.788 0.411 0.57 0.71 0.608 ...
  ..- attr(*, "dimnames")=List of 2

genefu documentation built on Nov. 1, 2018, 2:25 a.m.