A. Is the plotMDS function (from the limma package) based on PCA (Principal Component Analysis) or a PCoA (Principal Coordinate Analysis)?
B. What the values on the plot represent? Is it root-mean-square average or root-mean-square deviation (see below)?
In the limma paper published in Nucleic Acids Res at 2015 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402510/) it is stated that: "Distances between samples on the plot represent ‘leading fold change’, which is defined as the root-mean-square average* of the log-fold-changes for the genes best distinguishing each pair of samples. "
In the R manual it is stated that: "The distance between each pair of samples (columns) is the root-mean-square deviation (Euclidean distance) for the top ‘top’ genes. Distances on the plot can be interpreted as _leading log2-fold-change_, meaning the typical (root-mean-square) log2-fold-change between the samples for the genes that distinguish those samples."