Description Usage Arguments Details Value Author(s) References Examples
Implements Heller/Sampson method of testing multiple biological mediators simultaneously, controlling either FWER or FDR.
1 | medTest.SBMH(pEM,pMY,MCP.type="FWER",t1=0.05,t2=0.05,lambda=0)
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pEM |
Vector of size m (where m = number of mediators). Entries are the p-values for the E,M_j relationship. |
pMY |
Vector of size m (where m = number of mediators). Entries are the p-values for the M_j,Y|E relationship. |
MCP.type |
Multiple comparison procedure - either "FWER" or "FDR". |
t1 |
Threshold for determining the cutoff to be one of the top S_1 E/M_j relationships. |
t2 |
Threshold for determining the cutoff to be one of the top S_2 M_j/Y relationships. |
lambda |
Threshold for estimating the proportion of false positives. |
See Heller/Sampson paper for a more in-depth description of this method.
m x 1 matrix of either p-values (if MCP.type = "FWER") or q-values (if MCP.type = "FDR").
Ruth Heller, Joshua N. Sampson
Sampson JN, Boca SM, Moore SC, Heller R. FWER and FDR control when testing multiple mediators. Bioinformatics, 2018, 34(14), 2418-2424.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 | ##load dataset - details are given in the accompanying vignette
data(NavyAdenoma)
##the exposure of interest is the daily intake of fish
##the possible mediators are 149 normalized serum metabolite values
##the outcome of interest is colorectal adenoma case-control status
##get all metabolites
metabs <- colnames(NavyAdenoma)[6:154]
##get exposure/mediator relationships
pEM <- sapply(NavyAdenoma[,metabs],
function(m,e){coef(summary(lm(m ~ e)))[2,4]},
e=NavyAdenoma$Fish)
##get mediator/outcome relationship (conditional on exposure)
pMY <- sapply(NavyAdenoma[,metabs],
function(m,y,e){coef(summary(glm(y ~ m + e, family=binomial)))[2,4]},
y=NavyAdenoma$Adenoma, e=NavyAdenoma$Fish)
##perform mediation test for both FWER and FDR procedures
medTest.FWER <- medTest.SBMH(pEM, pMY, MCP.type="FWER")
##get smallest p-value and corresponding metabolite
min(medTest.FWER)
metabs[which.min(medTest.FWER)]
medTest.FDR <- medTest.SBMH(pEM, pMY, MCP.type="FDR")
##get smallest p-value and corresponding metabolite
min(medTest.FDR)
metabs[which.min(medTest.FDR)]
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