Model systems are a cornerstone of microbiology. However, despite microbiology’s heavy reliance on laboratory models, these systems are typically not analyzed systematically to improve their relevance. This limitation is a primary challenge to understand microbes’ physiology in natural environments. This study, which includes members of Georgia Tech's Center for Microbial Dynamics and Infection (CMDI), provides a proof of concept for generalizable approaches for model improvement using transcriptomic data of the pathogen Pseudomonas aeruginosa from sputum of patients with cystic fibrosis. The study's researchers include Marvin Whiteley, professor in the School of Biological Sciences, Georgia Tech Bennie H. and Nelson D. Abell Chair in Molecular and Cellular Biology, Georgia Research Alliance Eminent Scholar, and Co-Director, Emory-Children’s Cystic Fibrosis Center; Other School of Biological Sciences and CMDI researchers include Gina R. Lewin, postdoctoral scholar, and research scientists Daniel Cornforth and Francis Diggle.