Description: MACARRoN ( M etabolome A nalysis and C ombined A nnotation R anks for p R ediction of N ovel bioactives) is a tool for systematic analysis of microbiome-associated metabolomes for identification of novel, potentially bioactive small molecules. It leverages guilt-by-association i.e. covariance with a known metabolite to ecologically and biochemically annotate several thousand unknown features in metabolomes. To prioritize metabolites, it integrates ranks from multiple environmental or phenotypic indicators of bioactivity i.e. abundance and significant association with a condition (effect size and q-value). MACARRoN is currently being developed as an open source R package.