Most genetic sequencing of Mycobacteria, including Mycobacterium tuberculosis, has for historical reasons used short-read technology, often from Illumina. Whilst effective and economical, newer long-read technologies, as exemplified by Oxford Nanopore Technologies (ONT), confer several advantages, notability in terms of batch size and portability. In this paper we show that the described DNA extraction workflow enables ONT sequencing of Mycobacteria obtained after culturing in a MGIT tube and that there is little difference in the detected species, antibiotic resistances or relatedness between ONT- and Illumina-sequenced replicates.

In this preprint, Melody Parker as part of her DPhil, has analysed a series of infections in a neonatal intensive care unit. At the time there was concern that this could be an outbreak; if so the ICU team would want to improve their infection control measures. Whole genome sequencing can give you the really fine-grained resolution to be able to say that these two infections likely came from the same source or, more subtly for Enterobacterales, that the plasmid carrying the AMR gene in these two different species is identical and therefore is likely to have hopped from one to the other in the hospital environment.

Earlier this week the 46th Annual Congress of the European Society of Mycobacteriology was held in Verona, Italy. Around 210 scientists from over 40 countries attended and the University of Oxford, through the MMM Unit, was unusually well-represented with 11 of us travelling to Italy. Ruan Spies, Philip Fowler, Dylan Dissanayake, Rob Massey and Dylan Adlard all gave talks and Tim Walker chaired several sessions with others presenting posters. Yet again this was a great conference as it manages to combine excellent science but also encourages people to talk to one another.

As part of the "Enriching Engagement - funding, culture and institutional legacy" session at the Oxford Public & Community Engagement Conference on Thursday 11 June, Philip Fowler presented how the funding helped support BashTheBug, a citizen science project that run on The Zooniverse from 2017 to 2022. 

As part of the NIHR's "PPI In Action" series, Philip Fowler gave a webinar on Friday 22 May 2026 entitled: Running large online Citizen Science projects on the Zooniverse: my experience of setting up BashTheBug to help with our tuberculosis research. He talked about what problem we asked the citizen scientists to help us solve, how the Zooniverse works , from both the perspective of a citizen scientist and a scientist setting up a project, and the two subsequent Zooniverse projects that have been successfully run out of our Unit.

This paper is the start of us, as a group, using deep learning methods to predict antimicrobial resistance whilst taking into structural and chemical features. You can read a more detailed description in an earlier post and notably it is our first paper in a special issue for a while. Dylan Dissanayake did the research and was helped by Viki Brunner and Dylan Adlard, along with Joe Morrone from IBM Research.

Dylan successfully defended his DPhil on Friday 6 March, well done. From what he said his examiners, Professor Sam Sheppard and Associate Professor Louis Grandjean gave his work a thorough examination. As luck would have it we received the reviews from the last manuscript to come out of his thesis the day before..

In this preprint, we compare the differences when Mycobacterial samples are sequenced with either long- or short-read sequencing and show that long-read sequencing (as exemplified by Oxford Nanopore Technologies) is now comparable to short-read sequencing (e.g. Illumina). As we are focussed on clinical microbiological outputs, we compare the ability of both approaches to resolve the species and, if M. tuberculosis…

Zam Iqbal, at the University of Bath, led this epic study published today in Nature Methods where we assembled all SARS-CoV-2 genomes deposited in the European Nucleotide Archive before 2 March 2023. In total a staggering 4,395,655 samples were processed. Since SARS-CoV-2 was almost always sequenced using tiled amplicons (e.g. ARTICv3), he and his team wrote viridian which is a variant caller that identifies the amplicon scheme used and then uses that information to avoid making spurious calls.

Pleased and excited to be a small part of the Gram-Negative Antibiotic Discovery Innovator (Gr-ADI) consortium which was announced today. Gr-ADI is a join initiative between the Gates Foundation, Novo Nordisk Foundation, and Wellcome. Our project is headed by Dr Annette von Delft and you can read more about it here!

Viki successfully defended her DPhil thesis on Tuesday 9 December 2025 - well done! I always tell everyone they will enjoy the viva after half an hour or so and I hope she did. Her examiners were Professor Tim Walker and Associate Professor Conor Meehan.

This paper just published in Microbial Genomics examines how well our software tool, gnomonicus, predicts to which antibiotics a clinical sample that has been whole-genome sequenced is resistant. To do so, it implements the second edition of the WHO catalogue of resistance-associated mutations (WHOv2) which in turn we had to, in effect, translate from the original Excel and PDF report.

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…

In August 2022 seven laboratories across the world uploaded their SARS-CoV-2 genetics files for processing to an online cloud processing platform. Since then the pipeline that is run (the Tiled Amp…