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...

Complete Mutagenesis of the Genome and Proteome of ΦX174

The bacteriophage ΦX174 was the first genome to be sequenced and the first to be chemically synthesised. Here we present a complete map of the consequences of changing every nucleotide in the ΦX174 ge...

biorxiv.org

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.

bioRxiv Genomics@biorxiv-genomic.bsky.social · 2mo ago

OpenSplice: the impact of half a million mutations on the alternative splicing of 600 human exons https://www.biorxiv.org/content/10.64898/2026.05.22.727141v1

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/...

The allosteric landscape of the Src kinase

Comprehensive allosteric mapping prioritizes all possible druggable surface pockets in the Src kinase for allosteric inhibition.

science.org

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...

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins

Transcription factors (TFs) bind specific DNA sequences to control gene expression. Modulating TF activity is of considerable therapeutic interest but very few TFs have been successfully drugged. TF D...

biorxiv.org

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 👇

Alexandra Bendel@alexbendel.bsky.social · 12mo ago

I am happy to finally share this preprint of my PhD project in @guillaumediss.bsky.social lab at the FMI in Basel. We used ddPCA to map the genetic architecture of the entire human bZIP interaction network. www.biorxiv.org/content/10.1... Thanks to all our co-authors for the great collaboration!

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

Under which circumstances do genomic neural networks learn motifs and their interactions?

The use of neural networks to model genomic data in sequence-to-function scenarios has soared over the last decade. There remains much debate about whether these models are interpretable, either inher...

biorxiv.org

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

Allosteric and Energetic Remodeling by Protein Domain Extensions

Many functions of proteins are performed by independently folding structural units called domains. The structures of domains are conserved during evolution but they are not identical. For example, the...

biorxiv.org

🎲 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...

Allostery is a widespread cause of loss-of-function variant pathogenicity

Allosteric communication between non-contacting sites in proteins plays a fundamental role in biological regulation and drug action. While allosteric gain-of-function variants are known drivers of onc...

biorxiv.org

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

Wellcome Sanger Institute - Genomics Research Institute in Cambridge

We are a world-leading genomics research institute in Cambridge. Our work helps improve human health and understand life on Earth

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/...

Massively parallel genetic perturbation suggests the energetic structure of an amyloid-β transition state

The aggregation rates of >140,000 mutants reveal the energetic structure of an amyloid-β nucleation reaction transition state.

science.org

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]

The genetic architecture of an allosteric hormone receptor

Many proteins function as switches, detecting chemicals and transducing their concentrations into cellular responses. Receptor switches are key to the integration of environmental signals, yet it is n...

biorxiv.org

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...

The genetic architecture of an allosteric hormone receptor

Many proteins function as switches, detecting chemicals and transducing their concentrations into cellular responses. Receptor switches are key to the integration of environmental signals, yet it is n...

biorxiv.org

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

The genetic architecture of G-protein coupled receptor signaling

G-protein coupled receptors (GPCRs) are the most abundant class of human receptors and drug targets. The vast majority of GPCR drugs bind the conserved orthosteric pocket, which can lead to non-specif...

biorxiv.org

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

Charlie Pugh@cwjpugh.bsky.social · last yr.

New preprint in collaboration with @paulinanunezv.bsky.social supervised by @jonnyfrazer.bsky.social and Mafalda Dias – we propose a simple approach to improving zero-shot variant effect prediction in pre-existing protein and genome language models: 🧶 1/n www.biorxiv.org/content/10.1...

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

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

Jonathan Frazer@jonnyfrazer.bsky.social · last yr.

Very nice blogpost from @pascalnotin.bsky.social. You can catch him in Barcelona at www.varianteffect.org/mss2025/ #VariantEffect25 in a couple of weeks if you want to chat! Also, watch this space -- hoping to continue this discussion soon!

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/...

Massive experimental quantification allows interpretable deep learning of protein aggregation

xAI trained on >100,000 random peptides predicts and elucidates primary sequence determinants of aggregation.

science.org

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...

Centre de Regulació Genòmica (CRG)@crg.eu · 2y ago

We're excited to host the 8th annual meeting of the ‘Mutational Scanning Symposium’ in Barcelona. Experts from around will present their work, discuss new methods and provide insights on the burgeoning discipline. 21-23 May, with onsite & virtual options. #VariantEffect25

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)

Quantifying metabolites using structure-switching aptamers coupled to DNA sequencing

Nature Biotechnology - Metabolites can be quantified using a combination of aptamers and DNA barcodes.

rdcu.be