In previous work we've used "traditional" machine-learning approaches, like XGBoost, to learn and therefore predict which mutations in PncA confer resistance to pyrazinamide, one of the four first-line antibiotics used to treat tuberculosis. A key limitation is that because the data are presented in a tabular form, one in effect learns mutation-by-mutation rather than allele-by-allele. We can get away with this in…

Ruan Spies did a careful systematic analysis of the publicly-available pipelines that claimed to process raw genetics files from M. tuberculosis complex samples, including the pipeline available via EIT's GPAS which we have written. The preprint was posted back in January 2025 and the paper has just been published in the Lancet Microbe. There is a real range: 28 pipelines were identified but over half (16) were excluded for reasons ranging from being unable to install or execute (n=7), to no longer having a functioning website (n=2) or having a bug that was not fixed at the time of the study (n=1).

Received a lovely email from Dr Peter Cotgreave who is the Chief Executive of the Microbiological Society to say Dylan's manuscript where he created a resistance catalogue for bedaquiline was one of the most viewed papers in Microbial Genomics during September. Never had that before, but a nice surprise!

Last Thursday this work which we'd previously preprinted looking at looking at rifampicin-resistant subpopulations in clinical M. tuberculosis samples was published in JAC-Antimicrobial Resistance. If...

Last Thursday this work which we'd previously preprinted looking at looking at rifampicin-resistant subpopulations in clinical M. tuberculosis samples was published in JAC-Antimicrobial Resistance. If you want to know more please read the blog post we wrote when it was preprinted. A nice touch, however, was that this was just in time for Viki Brunner to include in her thesis as she submitted it the following day!

The CRyPTIC project carried out many exciting research projects but it never quite got around to building a catalogue of resistance- and susceptible-associated genetic variants in M. tuberculosis, in part because near the end of the project we donated our entire dataset to the Seq&Treat project who used it to build the first edition of the WHO catalogue of mutations in…

This work was carried out by Xibei Zhang, who is doing her PhD with Peter Coveney at UCL. It builds on earlier work I did using alchemical free energy methods to calculate whether individual mutations in the protein target of an antibiotic reduce how well the drug can bind, thereby conferring resistance. The method was first shown to work on…

The CRyPTIC project ran from 2016 to 2022 and collected >20,000 clinical samples from patients with tuberculosis. Each sample underwent whole genome sequencing and also was inoculated onto a 96-well plate containing 13 different antibiotics at a range of concentrations. We also collated some existing datasets and the project continued to collect data following the original data freeze in April 2020.

Most of us attended the third Diagnostics for Low- and Middle-Income Countries (Dx4LMICs) conference at Reuben College in Oxford over the last two days. I am a Fellow at Reuben College and helped our President, Professor Lord Lionel Tarassenko and several others, including Dylan Adlard, organise the conference. It was the biggest conference the college has held to date with about 110-120 attendees and we had to close registration a few weeks before and had a waiting list.

The CRyPTIC project ran from 2016 to 2022 and collected >20,000 clinical samples from patients with tuberculosis. Each sample underwent whole genome sequencing and also was inoculated onto a 96-well plate containing 13 different antibiotics at a range of concentrations. We also collated some existing datasets and the project continued to collect data following the original data freeze in April 2020.

Thanks to funding from the OxCoD4TB project, I am hiring a postdoctoral research associate. This consortium pulls together expertise from all over the University, including in diagnostics, data science, drug and vaccine design, preclinical testing and clinical testing and brings it to bear on tuberculosis (TB). The main aims of OxCoD4TB are to establish and validate a new TB therapeutics pipeline and discover and evaluate novel compounds and also drug and vaccine combinations.

Our paper describing how a convolutional neural network model can determine the minimum inhibitory concentrations (MICs) from a photograph of the 96-well plate after two weeks incubation has been published in the Computational and Structural Biology Journal. You can get the model, which is called TMAS, on GitHub here and there is a longer description here.

Several of us attended the 45th Annual Congress of the European Society of Mycobacteriology in Lisbon, Portugal. This is probably my favourite scientific meeting -- small, friendly and with plenty of time to talk, including organised social events. Viki Brunner, Dylan Adlard and Philip Fowler all had posters and there were another three posters from the MMM Unit. At the least minute we were offered a short ten minute talk as another speaker could not travel so we gladly accepted the chance and Philip Fowler presented some work analysing 56,306 Mycobacterial samples sequenced by UKHSA between 2016 and 2024. The main aim was to develop and validate an approach that can identify the species present.

Since clinical samples are usually grown in a MGIT tube for a while before some "crumbs" are harvested for DNA extraction, they are metagenomic in the sense that they can and do contain multiple colonies. This means we should expect subpopulations in our analysis but most bioinformatics tools and file formats inherently assume a homogenous sample with a single genome.

Very pleased to announce that I am a co-investigator on the recently announced Oxford4TB project that has been funded by the Ineos Oxford Institute for antimicrobial research (IOI). The project will received £5 million over three years and the main aim is to develop new therapies for multi-drug resistant tuberculosis. We will be guiding the selection of targets and leads using our large dataset of >50k clinical tuberculosis samples.

The CRyPTIC project ran from 2017 to around 2022 and in that time collected over 20,000 clinical samples of M. tuberculosis. Each sample underwent whole genome sequencing and phenotypic drug susceptibility testing (pDST); the minimum inhibitory concentrations (MICs) of 13 different antibiotics was tested using a bespoke 96-well broth microdilution plate. The project also aggregated previously published samples which has had pDST data and had undergone WGS.

The CRyPTIC project used bespoke 96-well broth microdilution plates to measure the minimum inhibitory concentrations (MICs) of 13 different antibiotics; to reduce the error in the measurements, photographs of each plate were taken after two weeks incubation and stored. Hence we have available over 20,000 images of M. tuberculosis growing on these plates along with MICs measured using a variety of approaches.

A catalogue recording whether individual mutations confer resistance or not to specified antibiotics is a necessary component of genetics-based clinical microbiology. Such catalogues need to be not only accurate but also meet a number of minimum requirements if they are to be used widely. Dylan Adlard, who is studying for his PhD, has developed a python package, catomatic, that automatically applies some logic evolved from the…

Back in the SARS-CoV-2 pandemic we worked closely with ORACLE Corp to build and deploy a bioinformatics pipeline in ORACLE Cloud that processes raw genetic files and infers what the consensus genome is and hence what lineage (e.g. BA.2) it belongs to. The heart of the pipeline is an amplicon-aware variant caller, viridian, that was written by Zamin Iqbal's group and there is a…