Conserved cross-domain protein-to-mRNA ratios enable proteome prediction in microbes

Deciphering the biology of natural microbial communities is limited by the lack of functional data. While transcriptomics enables gene expression profiling, mRNA levels often fail to predict protein abundance, the primary indicator of microbial function. Prior studies addressed this by calculating RNA-to-protein (RTP) conversion factors using conserved protein-to-RNA (ptr) ratios across bacterial strains, but their cross-species and cross-domain utility remained unknown. We generated comprehensive transcriptomic and proteomic data sets from seven bacteria and one archaeon spanning diverse metabolisms and ecological niches. We identified orthologous genes with conserved ptr ratios, enabling the discovery of RTP conversion factors that significantly improved protein prediction from mRNA, even between distant species and domains. This reveals previously unrecognized conservation in ptr ratios across domains and eliminates the need for paired proteomic data in many cases. Our approach offers a broadly applicable framework to enhance functional prediction in microbiomes using only transcriptomic data.