Raheleh Rahbari

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...

Sperm sequencing reveals extensive positive selection in the male germline - Nature A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

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 - Nature A systematic statistical genetics approach discovers CES drivers as hotspots of human de novo mutation and shows that clonal expansions in germline may both modulate the prevalence of disorders and lead to false-positive disease associations.

Hotspots of human mutation point to clonal expansions in spermatogonia

by @vseplyarskiy.bsky.social, Shamil Sunyaev et al

www.nature.com/articles/s41...

Thanks, Nuria! Also congratulations on your yet another beautiful paper: www.nature.com/articles/s41...

Sex and smoking bias in the selection of somatic mutations in human bladder - Nature Sex bias and association with smoking history identified in the landscape of driver mutations and clonal expansions in normal human bladder tissue may explain the higher bladder cancer risk in men and smokers.

🚨 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.

The impact of ancestral, genetic, and environmental influences on germline de novo mutation rates and spectra Nature Communications - Here the authors analyze de novo mutations in >10,000 parent-offspring trios and find that ancestry and smoking independently associate with mutation rate, but that...

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

The impact of ancestral, genetic, and environmental influences on germline de novo mutation rates and spectra - Nature Communications Here the authors analyze de novo mutations in >10,000 parent-offspring trios and find that ancestry and smoking independently associate with mutation rate, but that common genetic variants likely c...

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!

This is a great idea! I’d love to join plz.

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 ⬇️

Multiplex generation and single-cell analysis of structural variants in mammalian genomes Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) ...

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/...

Randomizing the human genome by engineering recombination between repeat elements We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into re...

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.

Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia - Nature A platform for mRNA lipid nanoparticle delivery to the placenta to treat pre-eclampsia is shown to improve fetal and maternal health in mice and has potential clinical applications in obstetric disorders and women's health.

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. 🧪

Diverse phage communities are maintained stably on a clonal bacterial host Bacteriophages are the most abundant and phylogenetically diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. In this study, w...

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...

This is an illustration with slides and lines connecting them that is to represent the Human Cell Atlas

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 .

Synthetic augmentation of cancer cell line multi-omic datasets using unsupervised deep learning Nature Communications - Multi-omics integration is often limited by data sparsity and heterogeneity. Here, the authors develop MOSA, a method designed to augment DepMap cell line data to...

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...

Somatic mutation and selection at epidemiological scale As we age, many tissues become colonised by microscopic clones carrying somatic driver mutations ([1][1]–[10][2]. Some of these clones represent a first step towards cancer whereas others may contribu...

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...

Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life - Nature Communications Clonal hematopoiesis becomes increasingly common with age. Here the authors track stem cell dynamics in monozygotic twins and provide evidence that clonal hematopoiesis in later life reflects weak sel...

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...