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Inigo Martincorena @imartincorena.bsky.social · 9h

I almost forgot I wrote a short review in 2019 saying this. genomemedicine.biomedcentral.com/articles/10.... The new supplementary notes have useful maths and historical references though.

Somatic mutation and clonal expansions in human tissues - Genome Medicine

Recent sequencing studies on healthy skin and esophagus have found that, as we age, these tissues become colonized by mutant clones of cells carrying driver mutations in traditional cancer genes. This comment summarizes these findings and discusses their possible implications for our understanding of cancer, ageing, and other diseases.

genomemedicine.biomedcentral.com

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Inigo Martincorena @imartincorena.bsky.social · 10h

Thanks Tami! Much appreciated. I agree. A supplementary note is hardly the best place for it. I have been meaning to write a review or two for a long time. But time seems to be eluding me.

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Inigo Martincorena @imartincorena.bsky.social · 10h

In our latest paper, I wrote 2 supplementary notes (5 and 6) to briefly recap classical models, starting with Armitage&Doll and moving onto models with different types of clonal expansions. Some readers may find them of interest. [4/4] static-content.springer.com/esm/art%3A10...

static-content.springer.com

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Inigo Martincorena @imartincorena.bsky.social · 10h

...the observation of large numbers of clones with driver mutations in normal tissues is perfectly consistent with (and indeed predicted by) multistage models of carcinogenesis dating from the 1950s. In the constant rush for new data, we seem to have forgotten invaluable lessons hidden in them [3/4]

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Inigo Martincorena @imartincorena.bsky.social · 10h

...or (2) the observation of driver mutations in normal tissues "proves" that non-mutational factors are needed to explain cancer (epigenetics, promotion, etc). Of course, many other factors are important, but ... [2/4]

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Inigo Martincorena @imartincorena.bsky.social · 10h

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 · 1d

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

www.nature.com

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Inigo Martincorena @imartincorena.bsky.social · 11h

Thanks Pierre. I was also struck by that finding... Very unexpected to me. Supplementary notes 5 and 6 try to expand on this, including modelling the types of aggregate clonal growth expected under different models of clonal growth. static-content.springer.com/esm/art%3A10...

static-content.springer.com

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Inigo Martincorena @imartincorena.bsky.social · 1d

Thanks Jeff!

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Reposted by Inigo Martincorena

Nuria Lopez-Bigas @nlbigas.bsky.social · 1d

🚨 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 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.

www.nature.com

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Inigo Martincorena @imartincorena.bsky.social · 1d

If you read the preprint, not a lot has changed. But if you didn't, here is a link to the original thread summarising our findings. Since then, NanoSeq has become a workhorse in our lab, unveiling a fascinating landscape of somatic evolution across tissues and diseases. bsky.app/profile/imar...

Inigo Martincorena @imartincorena.bsky.social · Nov 20

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...

www.medrxiv.org

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Inigo Martincorena @imartincorena.bsky.social · 1d

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

www.nature.com

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Reposted by Inigo Martincorena

Matthew Neville @mattneville.bsky.social · 1d

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.

www.nature.com

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Inigo Martincorena @imartincorena.bsky.social · Apr 26

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

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Inigo Martincorena @imartincorena.bsky.social · Mar 27

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

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Reposted by Inigo Martincorena

Tim Coorens @timcoorens.bsky.social · Mar 20

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 microdissected gastric glands from individuals with and without gastric cancer reveals distinct patterns of somatic mutations and provides insights into influen...

www.nature.com

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Reposted by Inigo Martincorena

Natalia Brzozowska @nataliabrzozowska.bsky.social · Mar 12

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...

www.nature.com

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Reposted by Inigo Martincorena

Jamie Blundell @jamie-blundell.bsky.social · Mar 6

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...

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Reposted by Inigo Martincorena

Chiraag Kapadia @chiraagkapadia.bsky.social · Mar 6

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...

www.nature.com

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Reposted by Inigo Martincorena

Mike Spencer Chapman @mikespencerchapman.bsky.social · Jan 15

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

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Inigo Martincorena @imartincorena.bsky.social · Jan 10

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

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Reposted by Inigo Martincorena

Dan Landau @landau.bsky.social · Jan 2

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 @ivanraimondi.bsky.social · Jan 2

🧬 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

Single-cell mapping of regulatory DNA:Protein interactions

Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibil...

biorxiv.org

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Inigo Martincorena @imartincorena.bsky.social · Dec 2

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...

uk.linkedin.com

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Reposted by Inigo Martincorena

Ruoyan Li @ruoyanli89.bsky.social · Nov 22

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.

www.nature.com

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Inigo Martincorena @imartincorena.bsky.social · Nov 22

Thanks!