A paper in Nature presents a detailed map of human chromosomes within the nucleus. This resource provides a foundation for an improved understanding of how the physical layout of human DNA is associated with biological expression. go.nature.com/4pI8knB 🧬 🧪

Our latest preprint revisits the classic model of mutation-selection balance. Do human recessive genes fit Haldane's 100-year old model? This work is by the wonderful @jonj-udd.bsky.social, and co-mentored by @jeffspence.github.io www.biorxiv.org/content/10.6...

AI agents for biology 🤖

GWAS has been an incredible discovery tool for human genetics: it regularly identifies *causal* links from 1000s of SNPs to any given trait. But mechanistic interpretation is usually difficult. Our latest work on causal models for this is out yesterday: www.nature.com/articles/s41... A short🧵:

It would be necessary to adapt ultra accurate sperm screening methods like NanoSeq method for sperm donors. This technology can identify low-frequency mutations unique to sperm, addressing critical gaps in standard screening methods, as highlighted by this unfortunate story!

A hidden evolutionary process has been uncovered in sperm — where certain harmful DNA changes are naturally favoured as men age. This gives some changes a competitive edge and increases the risk of genetic conditions. 🔬 Read here 👇 www.sanger.ac.uk/news_item/hi...

Read ‘Complex de novo structural variants are an underestimated cause of rare disorders’ from @sangerinstitute.bsky.social, @genomicsengland.bsky.social, @cuh.nhs.uk and collaborators in @natcomms.nature.com here: www.nature.com/articles/s41...

GLP-1 drugs can help people lose weight by quelling hunger queues. Nature reports on the work by scientists testing if these drugs can help to cut cravings for cigarettes, alcohol and opioids. 🧪

This study provides important results that show the sequence of cancer-driving mutations influences the likelihood of tumour development in the intestine, offering a deeper understanding of early cancer progression. 👇 www.sanger.ac.uk/news_item/or...

Hiring Senior Computational Postdoc to lead large-scale scRNAseq analysis for Project JAGUAR, one of the world’s most comprehensive single-cell immune resources from Latin American ancestries. If big data, global partnerships, human diversity and immune regulation excite you, apply! bit.ly/3XyFWrW

Metamorphosis is nature at its weirdest and historian Oren Harman has just written a beautiful book about it. Also check out this link for free access to the review I wrote about the book for this week's Nature: nature.com/articles/d41...

Struggling to navigate the grant-funding maze? Discover expert guidance and practical tips to help you transform your idea into a successful, funded project ✅ Read more: https://sangerinstitute.blog/2025/11/26/how-to-get-grant-funding-expert-advice-for-a-successful-application/

Transcription start sites show a strong influx of heritable variants arising in early development. Our new paper is now in Nat. Comms: www.nature.com/articles/s41... It would be interesting to see this effect in the new mosaic-mutation dataset from @r-rahbari.bsky.social and @isaacgs94.bsky.social.

NEWS: Study reveals how drug resistance develops early in targeted AML therapy A new study led by researchers at @rdm.ox.ac.uk has shown that resistance to a targeted treatment for acute myeloid leukaemia (AML) can develop much earlier than expected.

Honored to be recognized by @usnews.com as a 2025 #BestLeader alongside so many incredible colleagues and individuals I admire! www.usnews.com/news/best-le...

@kevinmonahan.bsky.social & I have an open clinical #PhD position between @stmarkshospital.bsky.social and @icr.ac.uk If you're interested in the biology of pre-cancer in the bowel & want to translate biology for cancer prevention this one could be for you... funded by the brilliant #40tude

Big, beautiful trees!! SMART-PTA for whole-genome+transcriptome on thousand of single cells from the normal human esophagus 🤯 Massively scaling up the power of scWGS to build deep phylogenies and chart somatic evolution from birth throughout life. www.biorxiv.org/content/10.1...

New preprint from another part of my PhD! 📝👇 Some mutations arise after fertilisation 🧬, so early they can appear in both a parent’s body and their germ cells. By analysing family trio genomes 👪, we built one of the largest catalogues of these “hidden” inherited variants yet. tinyurl.com/mvns2ytv

Another nice collaboration with @r-rahbari.bsky.social 's lab, PhD work by @isaacgs94.bsky.social on postzygotic mutations in the Genomics England 100,000 project.

If you saw preprint, biggest two updates are: Much improved discussion + variant calls now accessible If you'd like an accessible summary check out this great article from @mjflepage.bsky.social in New Scientist: For science thread read on! [2/n] institutions.newscientist.com/article/2499...

Now published! Our paper on: (1) Accurate sequencing of sperm at scale (2) Positive selection of spermatogenesis driver mutations across the exome (3) Offspring disease risks from male reproductive aging [1/n] www.nature.com/articles/s41...

Hotspots of human mutation point to clonal expansions in spermatogonia by @vseplyarskiy.bsky.social, Shamil Sunyaev et al www.nature.com/articles/s41...

🚨 New paper alert! Sex and smoking bias in the selection of somatic mutations in human bladder www.nature.com/articles/s41... by @raquelbmi.bsky.social, @ferriol.bsky.social et al (in collaboration with Rosana Risques lab in @uwmedicine.bsky.social)

This was a great collaboration between @geneticscam.bsky.social & @sangerinstitute.bsky.social, specifically the @hilarycmartin.bsky.social and @r-rahbari.bsky.social groups. We are also grateful to @genomicsengland.bsky.social for generating and supporting this fantastic resource.

A fun collaboration with @aylwyn-scally.bsky.social and @r-rahbari.bsky.social's groups using data from @genomicsengland.bsky.social . Paper here: rdcu.be/embGi

It's finally out people ✅🗞️! Check out the final version of our work exploring factors influencing the germline mutation rate and spectra on ~10,000 WGS family trios 🧬👨‍👩‍👦! www.nature.com/articles/s41...

A ridiculous amount of very careful work by @jahemker.bsky.social and coauthors gave a clear answer - one needs ultra-long and not just long reads to call SVs correctly in Drosophila. Now we are ready to quantify evolutionary impact of Drosophila SVs. Let us know what you think!

My lab at hiring! - we have TWO postdoc positions (one computational, one wet lab focussed) at Yale @yaleschoolofmed.bsky.social, working closely with our group members at University of Cambridge, UK @cambridgeuni.bsky.social Please help to spread the word! Adverts with full details below ⬇️

Now out in @science.org w/ @jshendure.bsky.social we present 'Genome-shuffle-seq': a method to shuffle mammalian genomes and characterize the impact of structural variants (SVs) with single-cell resolution in one experiment. www.science.org/doi/10.1126/...

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/...

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...

The distribution of highly deleterious variants across human ancestry groups https://www.biorxiv.org/content/10.1101/2025.01.31.635988v1

Freddie Whiting in our group wrote this thoughtful commentary on @karunamdphd.bsky.social's recent paper that explored cell state changes and plasticity in colorectal cancer evolution. He concludes we need to better understand epigenetic control of plasticity. authors.elsevier.com/c/1kTSf5Sx5g...

Two months ago, an amazing preprint by @r-rahbari.bsky.social 's group studied positive selection in sperm via direct sequencing. With her and @mattneville.bsky.social 's help, we compared findings—remarkably concordant! Our LoF genes show 16x more mutations, GoF sites 524x more.

A potential new mRNA-based therapy for pre-eclampsia is demonstrated in a mouse study published in Nature. The method involves targeted delivery of mRNA to the placenta to restore normal maternal blood pressure and improve foetal health. 🧪

Is it “winner-takes all” when the simplest living things compete? Check out my fresh publication on phage coexistence in Science and a thread below🧵 www.science.org/doi/10.1126/...

Spread the word! Registration for the "Mutations in Time and Space" conference is open. The meeting is all about the origins, patterns, and consequences of mutations across cells, individuals, populations, species. Abstract submission deadline is Jan 17th broadinstitute.swoogo.com/mits2025/597...

Join us for a webinar with Sarah Teichmann and Aviv Regev, co-founders of the Human Cell Atlas, who will discuss the latest research. Register here: https://go.nature.com/3OKQRKG Browse the collection: https://go.nature.com/4gnRFRj #AcademicSky 🧪

Applications open for several research positions here in Cambridge including evolutionary genetics, genomics and population genetics. www.jobs.cam.ac.uk/job/49389/

Does my mutation have the same impact as yours? Population genetics 🤠 🥸 🤓 🤡 meets single cell CRISPRi ⚡ ! www.biorxiv.org/content/10.1... Led by Claudia Feng, Oliver Stegle, Britta Velten, @sangerinstitute.bsky.social .

Thrilled to share our first dive into generative models, integrating 7 distinct omics to generate a complete Synthetic Cancer Dependency Map for +1,500 cancer cell lines! Excited for what’s ahead. rdcu.be/d1TgQ #GarnettLab #CMRI #ProCan #INESC-ID #IST @naturecomms.bsky.social

An early example is this beautiful study by @mattneville.bsky.social, @r-rahbari.bsky.social and cols applying exome NanoSeq to sperm and unveiling a rich landscape of selection in the male germline, which explains the high incidence of some developmental disorders. www.medrxiv.org/content/10.1...

Resharing here a recent X post. In this preprint, we introduce an improved version of NanoSeq, a duplex sequencing protocol with <5 errors per billion bp in single DNA molecules, and use it to study the somatic mutation landscape of oral epithelium in >1000 people. 1/ www.medrxiv.org/content/10.1...

Just in time for thanksgiving our paper is out ☄️ using fluctuating methylation clocks as barcodes we show that the variation in the hematopoietic stem cell pool that (in most of us) leads to clonal hematopoiesis in later life is likely present *before birth* 👉🏼 www.nature.com/articles/s41...