Question: Why shouldn't I interpret the hierarchical clustering tree in Loupe scDNA Browser as a single-cell phylogeny?
Answer: Although single cells or clonotypes can logically be represented by a phylogeny, unlike bulk tumor samples, which represent a combination of multiple cell lineages, the dendrogram in Loupe scDNA browser is not a single cell phylogeny.
Although variants of hierarchical clustering, such as neighbor-joining, are sometimes used in phylogenetics, the hierarchical clustering tree is based only on overall similarity of CNV profiles. Overall similarity doesn't equate to evolutionary history, and in many cases may be grossly misleading. Convergent evolution can result in overall similar CNV profiles among distant lineages, and large single mutations can cause closely related lineages to appear dissimilar. This can be further exacerbated when mutation rates or heterogeneity are unequal across the tree, which is expected for many datasets, such as a mix of tumor cells and healthy diploid cells. The dendrogram should thus be used as a starting point for identifying putative clonotypes or cells of interest, not to infer the relationships among them.