Do not miss this incredible paper from David Fernandez Antoran's team (with some contribution from my team). The paper introduces epithelioids as a powerful 3D culture system for 8 different human tissues, for longitudinal in vitro studies of human epithelia. Great thread from David below.

David Fernandez-Antoran@df-antoran.bsky.social · 2mo ago

🚨#Preprint alert! @antoranlab.bsky.social in close collaboration with @imartincorena.bsky.social lab www.biorxiv.org/content/10.6... How can we study human #epithelial tissues for months in the lab, while preserving their native structures and behaviour but without passaging?

Our autoimmunity paper is out today in final form and OA. We found a fascinating landscape of somatic evolution underpinning thyroid autoimmunity, where tens of B cell clones convergently lose immune checkpoints and some acquire 4-6 drivers over years of evolution. www.nature.com/articles/s41...

Excited to share our latest work in Nature. Applying single-molecule and single-cell DNA sequencing methods, we uncover an extraordinary landscape of somatic mutations in immune checkpoint genes in autoimmune B cells, suggesting that somatic mutations may be key to autoimmunity [1/n] rdcu.be/fdqbr

🚨 New paper from our lab just published in Nature🚨 www.nature.com/articles/s41... Discover how 🌱 tumour formation is shaped by tissue context from the very beginning. Cancer is not driven by genetics alone ✨Fantastic team led by Greta Skrupskelyte, Eduardo Rojo, @hariajith.bsky.social

Somatic genomics as a discovery engine for biomedicine - a Perspective in Cell www.sciencedirect.com/science/arti...

Somatic genomics as a discovery engine for biomedicine

Somatic mutations, or genetic changes occurring in cells after conception, are widespread in healthy tissues but are conventionally viewed as signs of…

sciencedirect.com

📰 News announcement! www.cancergrandchallenges.org/new-teams-an... We’re thrilled to welcome five world-leading scientific teams, each awarded up to £20 million, to take on some of the toughest unanswered questions in #CancerResearch. Find out more about the teams and their challenges.

$125m awarded to five visionary teams

$125m awarded to five visionary teams

cancergrandchallenges.org

We are very happy to see our study finally appear online @nature.com! This has been work of nearly 10 years in collaboration with the National Institute of Genome Medicine 🇲🇽, the National Cancer Institute 🇲🇽, the @sangerinstitute.bsky.social and others ⬇️ www.nature.com/articles/s41...

Ancestry and somatic profile indicate acral melanoma origin and prognosis - Nature

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples...

nature.com

How could a simple self-replicating system emerge at the origins of life? RNA polymerase ribozymes can replicate RNA, but existing ones are so large that their self-replication seems impossible. Could they be smaller? Excited to share our latest work in @science.org on a new small polymerase. 1/n

A small polymerase ribozyme that can synthesize itself and its complementary strand

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

science.org

A beautifully crafted summary of the extraordinary discovery in the lab of my @mrclmb.bsky.social colleague @philholliger.bsky.social of a tiny RNA that can replicate RNA.

Science Museum@sciencemuseum.org.uk · 6mo ago

Researchers have discovered a little RNA molecule - small enough to potentially form spontaneously, yet sophisticated enough to begin to copy itself - that could explain how life on Earth began over four billion years ago, Science Director @rogerhighfield.bsky.social reports: https://bit.ly/3ZvPS6s

Fully funded postdoc position in my team. CRUK and Wellcome Sanger Institute. Want to work on lung cancer + functional genomics? Only 1 more week to apply!💥

Matt Coelho@mattcoelho.bsky.social · 7mo ago

new year, new job?! Exciting postdoc position opening in my lab at the Wellcome Sanger Institute. Fully funded by CRUK sanger.wd103.myworkdayjobs.com/en-US/Wellco... find out more at www.coelho-lab.com

Colibactin-DNA interstrand crosslinks structure reveals DNA-damaging acitivity of colibactin that is linked to colorectal cancer #MicroSky www.science.org/doi/10.1126/...

The specificity and structure of DNA cross-linking by the gut bacterial genotoxin colibactin

Accumulating evidence has connected the chemically unstable, DNA-damaging gut bacterial natural product colibactin to colorectal cancer, including the identification of mutational signatures that are ...

science.org

What causes bladder cancer initiating mutations? Our paper in Science Advances asks the question: can BK virus infections of normal urothelium lead to the APOBEC3 mutational signatures found in bladder cancers? We found that they can!

Virus-induced APOBEC3 transmutagenesis in bladder cancer initiation

A model for hit-and-run viral carcinogenesis in the bladder.

science.org

A short thread. For years, I have been surprised by how much confusion our discovery of clones carrying cancer-driver mutations in normal tissues has caused in the cancer community. Typical questions like: (1) if you see these mutations in normal cells, are they really cancer drivers?... [1/4]

Inigo Martincorena@imartincorena.bsky.social · 10mo ago

Our latest work is out in Nature today. In this paper, 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 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)

Sex and smoking bias in the selection of somatic mutations in human bladder - Nature

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

nature.com

Our latest work is out in Nature today. In this paper, 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 www.nature.com/articles/s41...

Somatic mutation and selection at population scale - Nature

A new version of nanorate DNA&nbsp;sequencing, with an&nbsp;error rate&nbsp;lower than five errors&nbsp;per billion base pairs&nbsp;and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection&nbsp;and&nbsp;the generation of high-resolution&nbsp;selection&nbsp;maps across coding and non-coding sites for many genes.

nature.com

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...

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.

nature.com

I am speaking at #AACR25 this afternoon on our latest work on somatic mutations in normal tissues. If you are attending AACR, feel free to drop by and say hello. brnw.ch/21wRUZZ

If you are looking for an exciting postdoc position, please see below! Adrian Baez Ortega (a former member of the group) is starting an independent group at the University of Cambridge on the evolution of transmissible cancers and is recruiting. tinyurl.com/pdra-cambridge

The stomach is an organ unique in its function, environment and exposures. How does this affect the mutations that normal cells in the stomach acquire? What does this reveal about the origins of stomach cancer? These questions and more in our @nature.com paper: www.nature.com/articles/s41...

The somatic mutation landscape of normal gastric epithelium - Nature

Whole-gene sequencing of&nbsp;microdissected&nbsp;gastric glands from individuals with and without gastric cancer reveals distinct patterns&nbsp;of somatic mutations and provides insights into influen...

nature.com

Excited to share our new preprint demonstrating somatic rescue mutations in a genetic liver disease! [1/12] www.nature.com/articles/s41...

Selection for somatic escape variants in SERPINA1 in the liver of patients with alpha-1 antitrypsin deficiency - Nature Genetics

The expansion of clones with distinct SERPINA1 somatic mutants in the livers of alpha-1 antitrypsin deficiency (A1AT) patients is consistent with convergent evolution. These variants interfere with th...

nature.com

Delighted to share a major update on our work investigating age-related deceleration in clonal haematopoiesis. Takehome: Widespread and substantial deceleration in fitness with age! Amazing effort by PhD student Hamish MacGregor 💪 www.biorxiv.org/content/10.1...

Delighted to share my PhD thesis work is now published in @nature.com! This study tracks the journey of blood stem cells in aging mice, examining how the clonal dynmics of blood production change over time. A short 🧵1/n #aging #stemcells #clonalhematopoiesis www.nature.com/articles/s41...

Clonal dynamics and somatic evolution of haematopoiesis in mouse - Nature

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using labo...

nature.com

So pleased to have the paper out, available here: www.nature.com/articles/s41586-024-08423-8 For me this was discovery science as I had always hoped it would be. A lot of fun, and some proper detective work with plenty of twists & turns on the way. Brief thread below

A nice article covering some of the surprises in the field of somatic mosaicism in the last decade. As I say there: "Judging by the discoveries that we are making at the moment, the journey has only just started. I expect many surprises in the next few years." knowablemagazine.org/content/arti...

We are all mosaics

Picture your body: It’s a collection of cells carrying thousands of genetic mistakes accrued over a lifetime — many harmless, some bad, and at least a few that may be good for you.

knowablemagazine.org

Excited to share a major breakthrough from the lab! D&D-seq is a new technology that bridges a key gap in single-cell multi-omics/genomics : the ability to map DNA:Protein interactions (e.g., TFs or chromatin remodellers). Led by Ivan Raimondi, Wei-Yu Chi and Sang-Ho Yoon

@ivanraimondi.bsky.social · 2y ago

🧬 We’re excited to introduce D&D-seq, a single-cell technology that maps DNA:Protein interactions through molecular footprinting. Check it out here: biorxiv.org/content/10.1... #Genomics #Epigenetics

Quotient Therapeutics is looking for a new Head of Target Discovery, reporting to Peter Campbell, its new CSO. Lots of exciting somatic genomics in this role. uk.linkedin.com/jobs/view/he...

Thrilled to share our latest work on cutaneous T cell lymphoma. Check it out👇🏼 www.nature.com/articles/s41...

Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment - Nature Immunology

Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.

nature.com

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...

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...

medrxiv.org

Hello world! It is great to see so many friends and colleagues again. Feel free to follow me for updates on somatic mutation and selection in healthy tissues, ageing and disease.