ShortBRED is a system for profiling protein families of interest at very high specificity in shotgun meta'omic sequencing data. ShortBRED-Identify collapses proteins of interest into families, and then screens these families (as represented by consensus sequences) against 1) each other and 2) a comprehensive protein reference. ShortBRED-Identify then identifies short, distinguishing peptide sequences ("markers") for each protein family. This process is performed once for a given set of proteins of interest to produce a reusable marker set (see below for examples of pre-computed markers). ShortBRED-Quantify then screens a metagenome or metatranscriptome against a given marker set to profile the presence/absence and relative abundance of the associated proteins.