Read assignment is an important first step in many metagenomic analysis workflows, providing the basis for identification and quantification of species. However ambiguity among the sequences of many strains makes it difficult to assign reads at the lowest level of taxonomy, and reads are typically assigned to taxonomic levels where they are unambiguous. We explore connections between metagenomic read assignment and the quantification of transcripts from RNA-Seq data in order to develop novel methods for rapid and accurate quantification of metagenomic strains.