Cappable-seq allows for the capture of the 5′ end of primary transcripts. This is achieved by uniquely and enzymatically modifying the 5′ triphosphorylated end of RNA with a selectable tag. This enables a unique robust TSS determination in bacteria and microbiomes. In addition to and beyond TSS determination, Cappable-seq depletes ribosomal RNA and reduces the complexity of the transcriptome to a single quantifiable tag per transcript enabling digital profiling of gene expression in any microbiome. The procedure is schematically shown below.