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Deep Learning and Single Cell Phenotyping for Rapid Antimicrobial Susceptibility Testing

Zagajewski, A.; Turner, P.; Feehily, C.; El Sayyed, H.; Andersson, M.; Barrett, L.; Oakley, S.; Stracy, M.; Crook, D.; Nellaker, C.; Stoesser, N.; Kapanidis, A. N.

2022-12-09 infectious diseases
10.1101/2022.12.08.22283219 medRxiv
Show abstract

The rise of antimicrobial resistance (AMR) is one of the greatest public health challenges, already causing up to 1.2 million deaths annually and rising. Current gold-standard antimicrobial susceptibility tests (ASTs) are low-throughput and can take up to 48 hours, with implications for patient care. We present advances towards a novel, rapid AST, based on the deep-learning of single-cell specific phenotypes directly associated with antimicrobial susceptibility in Escherichia coli. Our models can reliably (80% single-cell accuracy) classify untreated and treated susceptible cells, across a range of antibiotics and phenotypes - including phenotypes not visually distinct to a trained, human observer. Applying models trained on lab-reference susceptible strains to clinical isolates of E. coli treated with ciprofloxacin, we demonstrate our models reveal significant (p<0.001) differences between resistant and susceptible populations, around a fixed treatment level. Conversely, deploying on cells treated with a range of ciprofloxacin concentrations, we show single-cell phenotyping has the potential to provide equivalent information to a 24-hour growth AST assay, but in as little as 30 minutes.

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