accuracy, and dynamic range of oligonucleotide sequences that can be determined. Recently, this focus has broadened to include post-transcriptional modifications, which have been shown to modulate the functions of biological RNAs in response to biochemical phenomena within the cell . Despite the precision inherent in many sequencing workflows, because many methods rely on complementary DNA to discern sequence information, sites and identities of post-transcriptional modifications can be lost. Although many chemical methods have been developed to interrogate individual modifications with high specificity, developments in mass spectrometry methods position it to tackle the challenges associated with characterization and localization of covalent modifications.