RefFreeCellMix: Reference-Free Cell Mixture Projection

In RefFreeEWAS: EWAS using Reference-Free DNA Methylation Mixture Deconvolution

Description

Reference-free cell-mixture decomposition of DNA methylation data set

Usage

RefFreeCellMix(Y,mu0=NULL,K=NULL,iters=10,Yfinal=NULL,verbose=TRUE)

Arguments

Y	Matrix (m CpGs x n Subjects) of DNA methylation beta values
mu0	Matrix (m CpGs x K cell types) of *initial* cell-type specific methylomes
K	Number of cell types (ignored if mu0 is provided)
iters	Number of iterations to execute
Yfinal	Matrix (m* CpGs x n Subjects) of DNA methylation beta values on which to base final methylomes
verbose	Report summary of errors after each iteration?

Details

Reference-free decomposition of DNA methylation matrix into cell-type distributions and cell-type methylomes, Y = Mu Omega^T. Either an initial estimate of Mu must be provided, or else the number of cell types K, in which case RefFreeCellMixInitialize will be used to initialize. Note that the decomposition will be based on Y, but Yfinal (=Y by default) will be used to determine the final value of Mu based on the last iterated value of Omega.

Value

Object of S3 class RefFreeCellMix, containing the last iteration of Mu and Omega.

Author(s)

E. Andres Houseman

References

Houseman, E. Andres, Kile, Molly L., Christiani, David C., et al. Reference-free deconvolution of DNA methylation data and mediation by cell composition effects. BMC bioinformatics, 2016, vol. 17, no 1, p. 259.

See Also

RefFreeCellMixInitialize

Examples

data(HNSCC)

# Typical use
Y.shortTest <- Y.HNSCC.averageBetas[1:500,]
Y.shortTest.final <- Y.HNSCC.averageBetas[1:1000,]
testArray1  <- RefFreeCellMixArray(Y.shortTest,Klist=1:3,iters=5,Yfinal=Y.shortTest.final)
testArray1
lapply(testArray1,summary)
sapply(testArray1,deviance,Y=Y.shortTest.final)

# Example with explicit initialization
testKeq2  <- RefFreeCellMix(Y.shortTest, mu0=RefFreeCellMixInitialize(Y.shortTest,K=2))
testKeq2
head(testKeq2$Mu)
head(testKeq2$Omega)

Example output

Loading required package: isva
Loading required package: qvalue
Loading required package: fastICA
Loading required package: JADE
Loading required package: quadprog
Fitting K = 1 
Fitting K = 2 
Fitting K = 3 
$`1`
Reference Free Deconvolution

Mu:  1000  cpgs x  1 cell types
Omega : 182  subjects x  1 cell types

$`2`
Reference Free Deconvolution

Mu:  1000  cpgs x  2 cell types
Omega : 182  subjects x  2 cell types

$`3`
Reference Free Deconvolution

Mu:  1000  cpgs x  3 cell types
Omega : 182  subjects x  3 cell types

$`1`
$`1`$Mu
              [,1]
Min.    0.02529775
1st Qu. 0.06074369
Median  0.10948784
Mean    0.29324068
3rd Qu. 0.56855922
Max.    0.97087057

$`1`$Omega
        [,1]
Min.       1
1st Qu.    1
Median     1
Mean       1
3rd Qu.    1
Max.       1

$`1`$MuCorr
     [,1]
[1,]    1


$`2`
$`2`$Mu
                 1          2
Min.    0.02243739 0.03243457
1st Qu. 0.05060754 0.08153978
Median  0.09094576 0.15396013
Mean    0.29125983 0.31162722
3rd Qu. 0.57323368 0.58227455
Max.    0.98530219 0.98835064

$`2`$Omega
                1             2
Min.    0.1149440 -8.673617e-19
1st Qu. 0.5221631  1.918575e-01
Median  0.6613921  3.261784e-01
Mean    0.6634123  3.208777e-01
3rd Qu. 0.7991188  4.613785e-01
Max.    0.9995492  8.173651e-01

$`2`$MuCorr
          1         2
1 1.0000000 0.9781331
2 0.9781331 1.0000000


$`3`
$`3`$Mu
                 1          2             3
Min.    0.01342084 0.03325373 -1.387779e-17
1st Qu. 0.03902011 0.08351233  9.282737e-02
Median  0.07518528 0.15670322  1.506967e-01
Mean    0.28730880 0.31119746  3.070024e-01
3rd Qu. 0.58662548 0.57753986  5.175947e-01
Max.    0.98162017 0.98268979  1.000000e+00

$`3`$Omega
                1         2          3
Min.    0.0000000 0.0000000 0.00000000
1st Qu. 0.4824314 0.1717646 0.04820658
Median  0.5794165 0.2947311 0.11713840
Mean    0.5702809 0.2974006 0.12008417
3rd Qu. 0.6884556 0.4247396 0.18082328
Max.    0.9284300 0.7664555 0.40828625

$`3`$MuCorr
          1         2         3
1 1.0000000 0.9778006 0.9399735
2 0.9778006 1.0000000 0.9140847
3 0.9399735 0.9140847 1.0000000


        1         2         3 
-4803.170 -5023.649 -5257.300 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
3.021e-05 2.323e-03 4.240e-03 6.051e-03 7.965e-03 4.841e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
5.643e-05 1.122e-03 2.203e-03 3.875e-03 4.752e-03 4.221e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
1.670e-06 5.311e-04 1.421e-03 2.856e-03 3.409e-03 3.617e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
1.901e-06 3.520e-04 1.035e-03 2.228e-03 2.656e-03 2.894e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
2.010e-07 3.039e-04 8.623e-04 1.806e-03 2.195e-03 2.268e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
4.375e-06 2.952e-04 7.385e-04 1.459e-03 1.797e-03 1.706e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
4.644e-06 2.906e-04 6.417e-04 1.197e-03 1.465e-03 1.323e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
7.100e-08 2.823e-04 5.772e-04 1.001e-03 1.245e-03 1.043e-02 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
2.416e-06 2.597e-04 5.119e-04 8.524e-04 1.082e-03 8.319e-03 
     Min.   1st Qu.    Median      Mean   3rd Qu.      Max. 
3.905e-06 2.403e-04 4.520e-04 7.295e-04 9.297e-04 6.746e-03 
Reference Free Deconvolution

Mu:  500  cpgs x  2 cell types
Omega : 182  subjects x  2 cell types
                    1          2
cg16762195 0.04959146 0.08017072
cg10691387 0.78690776 0.74396904
cg13878093 0.04967580 0.07733558
cg26845838 0.03605397 0.05237917
cg19335327 0.57701634 0.56974302
cg01169726 0.11689774 0.15872930
                      1         2
X5340127041_F 0.6665513 0.3131913
X5340127039_L 0.5056296 0.4786679
X5340127007_J 0.6726563 0.3046312
X5340127009_H 0.8439558 0.1519024
X5340127027_I 0.7580316 0.2179383
X5340127013_A 0.7700041 0.2271001

RefFreeEWAS documentation built on May 2, 2019, 5:52 a.m.