As we move towards a complete map of human variant effects, evaluating VEP and MAVE scores in clinically meaningful ways becomes essential. In work led by Yifei Shang and @jmarshlab.bsky.social, we explore mean evidence strength (MES) to quantify clinical utility after ACMG/AMP calibration.

Pinc is now available as a C program, eliminating interpreter overhead and substantially speeding up computation for large-scale structural analyses. It’s still under active development, so please reach out with any questions, feedback, or issues. 🔗 git.mpi-cbg.de/tothpetroczy... #alphafold

Great inaugural lecture by Joe. Honoured to see some of our joint work mentioned.

My first manuscript in MPI colours! With @tothpetroczylab.bsky.social, we show that AlphaFold PAE-derived contact probabilities are well calibrated to the fraction of true interface contacts across experimentally determined protein dimers. www.biorxiv.org/content/10.6...

SS18::SSX activates Polycomb target genes without BAF ❌ Instead, transcription relies on EP300 via the SS18 QPGY domain www.biorxiv.org/content/10.6... ➡️ Coactivator targeting emerges as a new therapeutic strategy in synovial sarcoma 🎯 Team work from @banitolab.bsky.social and @uoe-igc.bsky.social

The abstract deadline for Mutations in Time and Space 2026 closes in 3 weeks time. Sign up here: coursesandconferences.wellcomeconnectingscience.org/event/mutati... As well as thrilling science, the programme includes dinner at the beautiful King's College in Cambridge. @eventswcs.bsky.social

Our first foray into non-coding variation: structure-guided TF-DNA modelling with AlphaFold 3. Not a replacement for sequence-based predictors, but a complementary way to reason about mechanism. Nice collab with @simonbiddie.bsky.social academic.oup.com/nar/article/...

Can MAVEs and population-free VEPs be combined to improve variant classification? VEPs detect a broad range of pathogenic variants, while MAVEs give more conservative & decisive calls. Combined, they equitably reclassify >90% of VUS. Read more in our study on combining evidence from MAVEs and VEPs:

We have an exciting PhD opportunity through the EASTBIO programme, co-supervised with Diego Oyarzún. This project combines synthetic and systems biology to uncover the gene-regulatory circuitry hijacked in a cancer model. We’re looking for candidates with a strong interest in functional genomics.

acmgscaler: an R package and Colab for standardized gene-level variant effect score calibration within the ACMG/AMP framework academic.oup.com/bioinformati... 🧬🖥️🧪 github.com/badonyi/acmg... #Rstats

1/3 In this work on RyR1, led by Rolando, we (@marshlab.bsky.social) highlight the limitations of using ROC AUC alone to assess clinical utility. Future approaches should consider classification behaviour across the full score distribution. 📄 onlinelibrary.wiley.com/doi/epdf/10....

I'm stoked to be organising next year's MSS right here in beautiful Melbourne! We know Australia is very far away, and we're working hard to make sure we can support as many ECRs to attend as possible, so please do register and apply for a travel award!

1/8 Our new paper in Nature Communications explores how often pathogenic missense variants cause disease through loss-of-function (LOF), gain-of-function (GOF), or dominant-negative (DN) effects. 📄 nature.com/articles/s41...

Happy to share that 𝚊𝚌𝚖𝚐𝚜𝚌𝚊𝚕𝚎𝚛 is now on CRAN! 🎉 This means long-term stability and easy installation with: 𝚒𝚗𝚜𝚝𝚊𝚕𝚕.𝚙𝚊𝚌𝚔𝚊𝚐𝚎𝚜('𝚊𝚌𝚖𝚐𝚜𝚌𝚊𝚕𝚎𝚛') 🗞️ doi.org/10.1093/bioi... #rstats #acmg #varianteffect #MAVEs #VEPs #genomics

We’ve updated the acmgscaler manuscript following reviewer and community feedback. The R package now has a single calibrate() function, and the Colab interface is easier to use. 📄 Manuscript: www.biorxiv.org/content/10.1... 🧪 Colab: edin.ac/4mjzijp #rstats @theacmg.bsky.social

Why variant effect predictors and multiplexed assays agree and disagree https://www.biorxiv.org/content/10.1101/2025.07.31.667868v1

Congratulations to @gweykopf.bsky.social for her first first author manuscript, now on biorxiv. www.biorxiv.org/content/10.1... Many thanks to all involved - @wbickmor.bsky.social @mbadonyi.bsky.social @eliasfriman.bsky.social, Joe Marsh, Jasmine Nguyen, Mark Gorrell and others.

A knowledge-based distance metric highlights underperformance of variant effect predictors on gain-of-function missense variants https://www.biorxiv.org/content/10.1101/2025.07.23.666325v1

GWAS to mechanism: when non-coding is coding. Beautiful insightful science from @gweykopf.bsky.social @simonbiddie.bsky.social Joe Marsh and many colleagues. @uoe-igc.bsky.social @cmvm-edinburghuni.bsky.social www.biorxiv.org/content/10.1...

Thanks to #CCG2025 for the opportunity to present our work on `acmgscaler`, a standardised tool to convert functional scores into ACMG/AMP evidence strengths. #rstats

We've developed a method to align genetic variant effect scores with ACMG/AMP classification criteria. It has two key advantages: (1) no assumptions about score distributions, and (2) consistent outputs without user tuning.

So, how many genetic diseases come down to good ol’ loss-of-function in the targeted protein? Your estimate is probably too high:

Want to work with us on DNA methylation and rare genetic disease? Fully funded PhD project with deadline 16th May: www.findaphd.com/phds/project... Excited to collaborate with @hannahlong.bsky.social and Daria Bunina (@uoe-igc.bsky.social/@mdc-berlin.bsky.social). Please share 🙏 #epigenetics

Happy to have contributed to this work. As variant effect predictors become increasingly integral to genomic medicine, it is essential that their components and blueprints are accessible to researchers and developers.

Structure-informed classification of RyR1 variants highlights limitations of current predictors and enables clinical interpretation https://www.medrxiv.org/content/10.1101/2025.04.02.25325085v1

Tamina Lebek @lebektamina.bsky.social is a panellist in the last session of #biologists100. We took a photo of her and her little collaborator! Her key words are #BabiesInScience #PUFFFIN #NeighbourLabelling. Check out this interview with Tamina: thenode.biologists.com/the-sdb-bsdb...

1/ Excited to share our latest work on the "Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes". @marshlab.bsky.social @uoe-igc.bsky.social www.biorxiv.org/content/10.1...

Prof Joe Marsh and I have a PhD project as part of the 2025 Edinburgh Doctoral College Scholarship: "Integrating AI, Biophysical Modelling and Experimental Validation for Enhancer Variant Interpretation". Closing date for applications is 25 April 2025. Please get in touch if you are interested! 🧬🧠

Happy to see our predictive scores integrated into DECIPHER! We hope they will help clinicians uncover the molecular mechanisms driving dominant disease. Huge thanks to the team at @deciphergenomics.bsky.social for their support. A follow-up study is underway to improve predictions—stay tuned!

40 years ago all of Genbank was published in print form by NAR. The same format today would require over 4 light seconds of shelf space. To a year of progress in 2025.

Lagging a day behind, here's my #rstats solution to the day 6 of the 2024 #adventofcode. Part 2 brute forced, super slow, but with a progress bar so people know it's running. I'd really like to know what mathematical trick can speed this up. Link to R Colab: colab.research.google.com/github/badon...

my day 5 #rstats solution to the 2024 #adventofcode I have also created an R Colab for these solutions, so R-curious people can run them without having to install R: github.com/badonyi/adve...

my day 4 #rstat solution of the 2024 #adventofcode

my day 3 #rstats solution of the 2024 #adventofcode

my day 2 #rstat solution of the 2024 #adventofcode

my day1 #rstats solution of the 2024 #adventofcode