Fig. 1

Challenges to predicting drug resistance accurately from clinical specimens using current culture-dependent molecular diagnostics. The left panel depicts an expectorated sputum sample, which may not accurately represent the microbiologic diversity within the source patient. Culturing this sample (center panel) introduces further biases between faster- and slower-growing strains, such that faster-growing strains are over-represented within the cultured sample. Genomic DNA that is isolated and sequenced is input to computer algorithms that determine the genomic content, including the identification of drug-resistance mutations. However, disambiguating samples that contain mixed strains or detecting heteroresistance remains a computational challenge. The left panel was adapted from Ford et al. [170], with permission from Elsevier