Join us in Nottingham in September for the UK DNA replication meeting 🧬. Super EarlyBird deadline today and abstract deadline in 1 month. www.eventsforce.net/biochemsoc/f...

Having just taken this course, I highly recommend it.

EMBO Lab Leadership@embolableadership.bsky.social · 3mo ago

The EMBO Lab Leadership for #Postdocs online course running 16–18 June still has places open. Three days on the people side of running research: - interpersonal skills - tools for your development - clearer communication Sign up here: www.embolableadership.org/course/embol... #EMBOLabLead

A study, led by Hasan Çubuk, to identify how to improve diagnosis of the rare condition adenylosuccinate lyase (ADSL) deficiency, has created a framework which could be adapted for other recessive diseases. Read more here 👉 edin.ac/4tf5Zlj

New framework could help diagnose recessive rare diseases | Institute of Genetics and Cancer | Institute of Genetics and Cancer

A study to identify how to improve diagnosis of the rare condition adenylosuccinate lyase (ADSL) deficiency, has created a framework which could be adapted for other recessive diseases.

edin.ac

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.

bioRxivpreprint@biorxivpreprint.bsky.social · 4mo ago

Clinical evidence yield as a framework for evaluating computational predictors and multiplexed assays of variant effect https://www.biorxiv.org/content/10.64898/2026.03.27.714777v1

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

Mihaly Badonyi@mbadonyi.bsky.social · 5mo ago

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...

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

Institute of Genetics and Cancer@uoe-igc.bsky.social · 5mo ago

If you missed our Inaugural Lectures featuring Professor of Computational Protein Biology @jmarshlab.bsky.social and Professor of Computational Biology @csemple.bsky.social, you can catch up on their career journeys and research in genomics, cancer and computational biology here 👉 edin.ac/3P86GhY

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/...

A structure-guided approach to noncoding variant evaluation for transcription factor binding using AlphaFold 3

Abstract. Noncoding single-nucleotide variants (SNVs) that alter transcription factor (TF) binding can affect gene expression and contribute to disease. Se

academic.oup.com

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:

medRxivpreprint@medrxivpreprint.bsky.social · 8mo ago

Combining MAVEs and computational predictors improves variant classification across ancestries in hereditary cancer genes https://www.medrxiv.org/content/10.64898/2025.12.08.25341119v1

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.

EASTBIO - Dissecting CIC::DUX4 oncogenic circuitry through single-cell perturbation profiling and network inference at University of Edinburgh on FindAPhD.com

PhD Project - EASTBIO - Dissecting CIC::DUX4 oncogenic circuitry through single-cell perturbation profiling and network inference at University of Edinburgh, listed on FindAPhD.com

findaphd.com

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!

Atlas of Variant Effects Alliance@varianteffect.bsky.social · 10mo ago

📣Call for Abstracts for the Mutational Scanning Symposium! #VariantEffect26 🗓️ March 25-27, 2026 📍 Melbourne, Australia (and online!) 📝 Submit your abstract (deadline is Nov 2nd, 2025!) ➡️ Registration is also now open!! ℹ️ www.mss2026.org #FunctionalGenomics #Symposium #Australia #CallForAbstracts

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...

Institute of Genetics and Cancer@uoe-igc.bsky.social · 10mo ago

Find out more about a new online tool which allows researchers and clinicians to estimate likely disease mechanisms for sets of mutations, supporting better diagnosis and personalised medicine 👉 edin.ac/3W5ykw3 @mbadonyi.bsky.social @jmarshlab.bsky.social

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

acmgscaler: An R package and Colab for standardised gene-level variant effect score calibration within the ACMG/AMP framework

A genome-wide variant effect calibration method was recently developed under the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/A...

biorxiv.org

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.

Disease-associated genetic variants can cause mutations in tissue-specific protein isoforms

Genetic variants can cause protein-coding mutations that result in disease. Variants are typically interpreted using the reference transcript for a gene. However, most human multi-exon genes encode al...

biorxiv.org

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.

bioRxiv Bioinfo@biorxiv-bioinfo.bsky.social · last yr.

acmgscaler: An R package and Colab for standardised gene-level variant effect score calibration within the ACMG/AMP framework https://www.biorxiv.org/content/10.1101/2025.05.16.654507v1

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

Mutant Proteins Classified

science.org

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

Fully Funded PhD Studentship in Human Genetics, Genomics and Disease: Dissecting DNMT3B functions in Immunodeficiency-centromeric instability facial anomalies syndrome at University of Edinburgh on Fi...

PhD Project - Fully Funded PhD Studentship in Human Genetics, Genomics and Disease: Dissecting DNMT3B functions in Immunodeficiency-centromeric instability facial anomalies syndrome at University of E...

findaphd.com

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.

Joe Marsh@jmarshlab.bsky.social · last yr.

New paper out in Genome Biology! 🎉 We lay out best-practice guidelines for releasing variant effect predictors, developed through the Atlas of Variant Effects Alliance @varianteffect.bsky.social Open, interpretable, and clinically useful VEPs are the goal. 📄 doi.org/10.1186/s130...

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...

Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes

Molecular disease mechanisms caused by mutations in protein-coding regions are diverse, but they can be broadly categorised into loss-of-function (LOF), gain-of-function (GOF), and dominant-negative (...

biorxiv.org