fcrosMod function

Search for differentially expressed genes or to detect recurrent copy number aberration probes

Implementation of a method based on fold change rank ordering statistics to search for differentially expressed genes or to detect chromosomal recurrent copy number aberration probes. This function should be used with a matrix of fold changes or ratios from biological dataset (microarray, RNA-seq, ...). The function fcrosMod() is an extention of the function fcros() to a dataset which does not contain replicate samples or to a dataset with one biological condition dataset. Statistics are associated with genes/probes to characterize their change levels.

fcrosMod(fcMat, samp, log2.opt = 0, trim.opt = 0.25)

Arguments

• fcMat: A matrix containing fold changes or ratios from a biological dataset to process for searching differentially expressed genes or for detecting recurrent copy number aberrations regions. The rownames of fcMat are used for the output idnames.
• samp: A vector of sample label names which should appear in the columns of the matrix fcMat: samp.
• log2.opt: A scalar equals to 0 or 1. The value 0 (default) means that values in the matrix "fcMat" are expressed in a log2 scale: log2.opt = 0
• trim.opt: A scalar between 0 and 0.5. The value 0.25 (default) means that 25% of the lower and the upper rank values for each gene are not used for computing the statistic "ri", i.e. the interquartile range rank values are averaged: trim.opt = 0.25

Details

The label names appearing in the parameter "samp" should match some label names of the columns in the data matrix "xdata". It is not necessary to use all label names appearing in the columns of the dataset matrix.

Returns

This function returns a data frame containing 8 components - idnames: A vector containing the list of IDs or symbols associated with genes

• ri: The average of ordered rank values associated with genes in the dataset. These values are rank statistics leading to the f-values and the p-values.

• FC2: The robust fold changes for genes in matrix "fcMat". These fold changes are calculated as a trimed mean of the values in "fcMat". Non log scale values are used in this calculation.

• f.value: The f-values are probabilities associated with genes using the "mean" and the "standard deviation" ("sd") of values in "ri". The "mean" and "sd" are used as a normal distribution parameters.

• p.value: The p-values associated with genes. The p-values are obtained using a one sample t-test on the fold change rank values.

• bounds: Two values, which are the lower and the upper bounds or the minimum and the maximum values of the non standardized "ri".

• params: Three values, which are the estimates for the parameters "delta" (average difference between consecutive ordered average of rank) "mean" (mean value of the "ri") and the standard deviation ("sd") of the "ri".

• params_t: Three values, which are theoretical levels for the parameters "delta", "mean" and "sd".

Author(s)

Doulaye Dembele doulaye@igbmc.fr

References

Dembele D, Analysis of high biological data using their rank values, Stat Methods Med Res, accepted for publication, 2018

Examples

data(fdata);
   rownames(fdata) <- fdata[,1];

   cont <- c("cont01", "cont07", "cont03", "cont04", "cont08");
   test <- c("test01", "test02", "test08", "test09", "test05");
   log2.opt <- 0;
   trim.opt <- 0.25;

   # perform fcrosMod()
   fc <- fcrosFCmat(fdata, cont, test, log2.opt, trim.opt);
   m <- ncol(fc$fcMat)
   samp <- paste("Col",as.character(1:m), sep = "");
   fc.val <- cbind(data.frame(fc$fcMat))
   colnames(fc.val) <- samp
   rownames(fc.val) <- fdata[,1]

   af <- fcrosMod(fc.val, samp, log2.opt, trim.opt);

   # now select top 20 down and/or up regulated genes
   top20 <- fcrosTopN(af, 20);
   alpha1 <- top20$alpha[1];
   alpha2 <- top20$alpha[2];
   id.down  <- matrix(0,1);
   id.up <- matrix(0,1);
   n <- length(af$FC);
   f.value <- af$f.value;

   idown <- 1;
   iup <- 1;
   for (i in 1:n) {
       if (f.value[i] <= alpha1) { id.down[idown] <- i; idown <- idown + 1; }
       if (f.value[i] >= alpha2) { id.up[iup] <- i; iup <- iup + 1; }
   }

   data.down <- fdata[id.down[1:(idown-1)], ];
   ndown <- nrow(data.down);
   data.up <- fdata[id.up[1:(iup-1)], ];
   nup <- nrow(data.up);

   # now plot down regulated genes
   t <- 1:20;
   op = par(mfrow = c(2,1));
   plot(t, data.down[1, 2:21], type = "l", col = "blue", xlim = c(1,20),
        ylim = c(0,18), main = "Top down-regulated genes");
   for (i in 2:ndown) {
       lines(t,data.down[i, 2:21], type = "l", col = "blue")
   }

   # now plot down and up regulated genes
   plot(t, data.up[1,2:21], type = "l", col = "red", xlim = c(1,20), 
       ylim = c(0,18), main = "Top up-regulated genes");
   for (i in 2:nup) {
       lines(t, data.up[i,2:21], type = "l", col = "red")
   }
   par(op)