In this preprint, which Alice has been working on for several years, we show how alchemical free energy methods can predict whether an amino acid mutation confers resistance to an antitubercular, but only in cases where the change in binding free energy is large. This is mainly because the confidence limits on the change in […]
Oliver Adams successfully elucidated the structure of the M. tuberculosis MmpL3 membrane transporter using cryo-EM and this has recently been published online in Structure. This was the main aim of his PhD studies in Simon Newstead‘s group in the Department of Biochemistry here in Oxford. It is an important protein structure since although other MmpL3 […]
Through the CompBioMed2 EU Centre of Excellence project I have funding to appoint a postdoctoral researcher to develop machine-learning models to predict whether an infection is susceptible to an antibiotic. The need for predictive methods, such as these, will grow in the coming years as more of clinical microbiology transitions to using genetics to infer […]
I’ve been working on this for the last few months and very happy that we can now share our plans. Through a very generous donation by ORACLE, a group of researchers led by ModMedMicro at Oxford, are developing a cloud-based clinical microbiology genetics processing service, called the Global Pathogen Analysis System (GPAS). GPAS is still […]
In this preprint we examine 14,151 clinical isolates drawn from the CRyPTIC dataset. Each isolate had its minimum inhibitory concentration (MIC) to bedaquiline and clofazimine measured and hence we were able to identify the transcription regulator Rv0678, as the current main source of elevated MICs to both these drugs. Lindsay Sonnenkalb, who is studying for her […]
In this preprint, the CRyPTIC project proposes the maximum value of minimum inhibitory concentration (MIC) for 13 different anti-TB drugs below which a sample can be considered to be ‘genotypically wild-type’. It is necessary to establish these values, called epidemiological cutoff values (ECOFFs or ECVs), so that the MICs measured can be converted into binary […]