Ben Lehner

Conservation and divergence in the allosteric architectures of five human protein kinases. Excited to share our new preprint by @carlafolgado.bsky.social @tonibeltran.bsky.social @sangerinstitute.bsky.social @crg.eu @ibv-csic.bsky.social www.biorxiv.org/content/10.6...

Allostery is a widespread cause of loss-of-function variant pathogenicity by @xt117.bsky.social @sangerinstitute.bsky.social www.nature.com/articles/s41...

1st genome sequenced (Sanger 1977), 1st genome synthesised (Venter 2003), 1st genome + proteome fully mutated (Huijin Xiangua 2026!) @crg.eu @sangerinstitute.bsky.social Complete Mutagenesis of the Genome and Proteome of ΦX174 www.biorxiv.org/content/10.6...

Congratulations to CRG's @benlehner.bsky.social on receiving the 2026 Premio Rei Jaume I for Biomedical Research. The award recognises his pioneering discoveries on genetic variation, evolution and disease, helping transform our understanding of biology and human health. #genomics #genetics #CRG

Excited to release #OpenSplice - the impact of >500,000 mutations on the alternative splicing of 600 human exons www.biorxiv.org/content/10.6... Led by @gioia-quarantani.bsky.social + funded by @opentargets.org ‬ @sangerinstitute.bsky.social @crg.eu #cshlsymp26 #RNA2026 @rnasociety.bsky.social

Introducing OpenSplice, an atlas of splice-altering variants and the largest systematic analysis of splicing regulatory variants OpenSplice quantifies the impact of 590,000+ variants on the splicing of 608 alternatively spliced exons, and is out now on bioRxiv 🧬🖥️ www.biorxiv.org/content/10.6...

1\ Excited to finally share some of my PhD work: OpenSplice! We measured how >590,000 mutations affect exon inclusion across 600 human exons, creating a resource to study splicing regulation, benchmark variant effect predictors, and support variant interpretation.

Great collaboration between @genomedatalab.bsky.social at @irbbarcelona.org / @bric-ucph.bsky.social and the @benlehner.bsky.social group at @crg.eu / @sangerinstitute.bsky.social 👉Read our NMDetective-AI study www.biorxiv.org/content/10.6...

AI x BIO 2026, 8-10 June Submit an abstract now! >450 registered last year coursesandconferences.wellcomeconnectingscience.org/event/ai-x-b...

Wow. Catalonia has more active clinical trials than the entirety of the UK or Germany. That's wild. From the latest @biocat.cat annual report.

The allosteric landscape of the Src kinase by Toni Beltran, @ajfaure.bsky.social , @crg.eu @sangerinstitute.bsky.social @alloxbio.bsky.social www.science.org/doi/10.1126/...

Looking to start your lab in generative biology / AI? Come join us at the @sangerinstitute.bsky.social Sanger is core-funded so you can generate data at scale to train the next generation of models and understanding. Design/Engineering/Chemistry/Proteins/Pathways! pls RT tinyurl.com/GenGenFaculty

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins by @XianghuaLi2 Are Transcription Factors really 'undruggable'? www.biorxiv.org/content/10.1...

Latest pre-print from our lab is out. Great work by @alexbendel.bsky.social and team. Full deep mutational scan of an entire human protein interaction domain family 2M quantitative measurement of protein-protein interaction -> deep learning model to predict PPI from sequence More details 👇

Under which circumstances do genomic neural networks learn motifs and their interactions?https://www.biorxiv.org/content/10.1101/2025.07.25.666754v1

New preprint from the allostery team www.biorxiv.org/content/10.1...

🎲 Our paper on the genetics, energetics, and allostery in proteins with randomized cores and surfaces is out today @science.org! 🧬 By charting a protein’s sequence universe, we could rationalize which versions were kept through evolution – and why many stable ones were not.

New preprint: Allostery is a widespread cause of loss-of-function variant pathogenicity by the great @xt117.bsky.social biorxiv.org/content/10.1...

Only a few days left to apply to become a group leader in our Generative Biology programme at @sangerinstitute.bsky.social www.sanger.ac.uk

Arriving at the airport to fly to an AI conference and this happens #AIxBio25

The evolution of allostery in a protein family. Aina's new preprint containing seven complete comparative allosteric maps biorxiv.org/content/10.1...

Alzheimer’s disease 🧠starts with a molecular domino effect - but what triggers the first piece to fall? In our new study we cracked open the black box of early protein aggregation, and the findings could reshape how we fight neurodegeneration. 🧵👇 www.science.org/doi/10.1126/...

1 plant hormone receptor ☘️ 3,500 mutants, to single-site saturation 🧬 >45,000 binding and abundance measurements 📶 Very happy to present our latest work – where deep mutational scanning meets the world of small molecules.

 www.biorxiv.org/content/10.1...

 With @benlehner.bsky.social [1/7]

Shoutout to the Maxi @maxstammnitz.bsky.social for pioneering dose-response methods and check out his pre-print too: www.biorxiv.org/content/10.1...

GPCR-MAPS is now live! www.biorxiv.org/content/10.1... A new platform for high resolution functional mapping of GPCRs with massive mutagenesis. We identify the core activation network, residues involved in biased signaling, and generate >7,000 full dose response curves. With @benlehner.bsky.social

Want to improve your protein or genomic language model’s performance at zero-shot variant effect prediction? We propose a simple adjustment to likelihood-based predicton

Our "Atlas of Variant Effects 2030 Roadmap" is live: zenodo.org/records/1542... 1/n

Countdown officially started! #VariantEffect25 @varianteffect.bsky.social

Come and join us! We’re hiring a new Group Leader in Generative Biology at the @sangerinstitute.bsky.social Building AI models or the data to train them? Core funding of >$130M a year for a faculty of ~30. www.nature.com/naturecareer... acrobat.adobe.com/id/urn:aaid:... pls RT!

We quantify the aggregation of >100,000 random protein sequences to train CANYA, a convolution-attention hybrid neural network to predict aggregation from sequence. With @bennibolo.bsky.social www.science.org/doi/10.1126/...

Deadline for abstract submissions and early bird reg for #VariantEffects25 is 1 March 2025. Organised by @bennibolo.bsky.social @jonnyfrazer.bsky.social @benlehner.bsky.social @muffley.bsky.social @muffley.bsky.social and Mafalda Dias. More info: events.ibecbarcelona.eu/mutational-s...

Delighted to share our latest paper describing a method to read the levels of hundreds of metabolites or drugs in parallel using DNA sequencing. This method, which we call ‘smol-seq’ (Small MOLecule sequencing), harnesses the power of DNA sequencing for metabolite detection: rdcu.be/d8xLv (1/6)

3 great computational positions available at @alloxbio.bsky.social to work with the great @ajfaure.bsky.social @juliadiumenge.bsky.social and team

At ALLOX @alloxbio.bsky.social in Barcelona we now have 3 computational positions available! 📌Structural Bioinformatics Scientist 👉 tinyurl.com/3rs46j4t 📌Platform Bioinformatician 👉 tinyurl.com/nyvazbke 📌Computational Chemist 👉 tinyurl.com/5n6vpem3 Apply or repost to help us spread the word 🙏

I am incredibly excited to announce that our project with @benlehner.bsky.social, @thomaswilhelm-blue.bsky.social, and the @crg.eu #TBDO has been awarded an ERC Proof of Concept Grant from @ercresearch.bsky.social! Huge thanks to everyone involved for their ongoing support – let's boost the science!

If you’d like to work on such projects, our team is hiring postdocs! We are part of the new Generative and Synthetic Genomics programme with @benlehner.bsky.social and Jussi Taipale, combining data generation at scale with AI to solve biology.Check out sanger.wd103.myworkdayjobs.com/en-US/Wellco...

We're delighted to share our work on scrambling the human genome using prime editing, repetitive elements, and recombinases in @science.org , led by @jonaskoeppel.bsky.social , @f-raphael.bsky.social , with @proftomellis.bsky.social and George Church. www.science.org/doi/10.1126/...

Nice highlighting of @taylor-mighell.bsky.social's GPCR pharmacochaperone preprint by @dereklowe.bsky.social @science.org www.biorxiv.org/content/10.1...

We are happy to share our enhancer scramble story, a strategy to create hundreds of stochastic deletions, inversions, and duplications within mammalian gene regulatory regions and associate these new architectures with gene expression levels 🧵 www.biorxiv.org/content/10.1...

@crg.eu (winter) commute

Missense mutations are responsible for many heritable genetic disorders. Researchers led by @benlehner.bsky.social are carrying out large-scale experiments to understand why. Unstable proteins are emerging as a clear mechanism of action. Today in @elpais.com by @manuelansede.bsky.social.

Introducing Human Domainome v1, the largest and most comprehensive library of human protein variants to date, which maps the effects of +500K mutations across 522 domains. The study by @benlehner.bsky.social and Toni Beltran is out now in @nature.com. Illustration by @queralttolosa.bsky.social.

What a way to start 2025! Our spliceosome blueprint has been recognized by @forbes.com as one of the “Top Five Breakthroughs of 2024”. Huge thanks to my colleagues and my mentor Juan Valcarcel at @crg.eu #Biotech #Spliceosome #RNA #Innovation www.forbes.com/sites/alexkn...

One lovely thing about living and working in Barcelona: flying home and, on the final approach, catching a panoramic view of our daily routine.

Can a single small molecule rescue the stability of nearly all mutations in a protein? Our new preprint by Taylor Mighell www.biorxiv.org/content/10.1... thread on the other place: x.com/taylor_mighe...

It is always best to get scooped on a project before you put much work on it. Really cool preprint by Taylor Mighell and Ben Lehner on the effect of binder molecules on general rescue effect of destabilizing variants. Should work with protein binders as well. www.biorxiv.org/content/10.1...

We have two open PhD positions in my group at @crg.eu. We are seeking candidates with a background in computational and/or molecular biology, and with a broad interest in evolutionary biology, gene regulation, and comparative genomics. 📅Apply before January 12 here: www.crg.eu/en/content/t...

last couple days to apply (for free! from anywhere in the world!) to the Sanger 2025 PhD Programme — Deadline: 28th November 2024 (09:00 GMT) For more info, visit www.sanger.ac.uk/about/study/...

Excited to announce that I will start my group at @crg.eu in Barcelona next April! We will decode and engineer cell fates using stem cell models, perturbation screening and single-cell multiomics. Looking forward to the new chapter ahead!

Big 🧬 news this week: we have launched the first Joint Program on Evolutionary Medical Genomics. Spearheaded by @mirimiam.bsky.social, Barcelona researchers will study and exploit the vast genomic diversity of life on Earth to enhance precision medicine. Full story in @elpais.com