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embl.wd103.myworkdayjobs.com

Last but not least, if you're interested in somatic mutations, new technologies and computational genomics - we're hiring a postdoc in my brand new lab @emblebi.bsky.social! Reach out if interested or you have any questions, and apply here: embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

Postdoctoral Fellow in Coorens Group

We are looking for a motivated and talented postdoctoral-level researcher with experience in genomic analyses to join the newly established Coorens group at EMBL-EBI. We study how normal cells in diff...

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This effort would be impossible without the work of many hundreds of people, including the scientists, the NIH staff, and - of course - the donors and their family. A very exciting time to study somatic evolution and I can't wait to see what the next years bring.

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SMaHT will generate massive amounts of data, including short-read, long-read, duplex, single cell DNA, and donor specific assemblies, and much more. Check out our stellar data platform (data.smaht.org), courtesy of our Data Analysis Center in Peter Park's lab - watch this space for future data!

data.smaht.org

SMaHT Data Portal

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Underpinning the efforts of the Network is a set of 150 donors from across the US and age range, collected by the NDRI, with many tissues samples for each donor - an absolutely unique collection and momentous effort. Also more info at our consortium website: smaht.org

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The SMaHT Network, funded by the NIH Common Fund, has over 300 members from over 50 different institutions all working together on developing new tools and technologies to detect somatic variation, analysing the data in the best way possible, and generating a reference catalog of mosaicism

The cells in our bodies constantly acquire mutations. But what are the patterns of mutations across tissues? How do mutations in normal cells lead to cancer and disease? These are questions we will tackle within the Somatic Mosaicism across Human Tissues (SMaHT) Network, now described in @nature.com

The Somatic Mosaicism across Human Tissues Network - Nature

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

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Reposted by Tim Coorens

CiMUS @cimususc.bsky.social · 27/06/2025

Upcoming #CiMUSseminar on Monday ⤵️ 🗣 Dr. @timcoorens.bsky.social from @ebi.embl.org : 🧪 "Somatic mutations across normal tissues: past, present, future" 📅 June 30, 1 PM 📍 Theatre room, CiMUS #RedeCiGUS #FondosEuropeos ‪@mobilegenomes.bsky.social‬ @usc.gal ‪

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Reposted by Tim Coorens

Geoff Macintyre @gmaci.bsky.social · 23/06/2025

🚨Chemo treatment upgrade!🚨 Check out our approach to modernise chemotherapy treatment published today in @natgenet.nature.com. From @cniostopcancer.bsky.social #TailorBio @cruk-ci.bsky.social www.nature.com/articles/s41... More details 👇

Kamila Naxerova @naxerova.bsky.social · 21/05/2025

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Reposted by Tim Coorens

Social media grump Kamila has finally made it onto Bluesky! Please check out my new perspective on metastasis evolution in @natrevcancer.nature.com if you need a reprieve from the news. I tried my best to develop some new conceptual thoughts here, you be the judge whether I succeeded.

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Reposted by Tim Coorens

smahtnetwrk.bsky.social @smahtnetwrk.bsky.social · 16/05/2025

Keeping you in the loop! ➰ Our Linktree includes all SMaHT websites and social media accounts for easy and consistent access. Find all our social media accounts in one place: linktr.ee/smahtnetwork

linktr.ee

SMaHT Network | Instagram, Facebook | Linktree

Aiming to transform our understanding of somatic mosaicism.

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Reposted by Tim Coorens

Vijay G. Sankaran @bloodgenes.bsky.social · 01/05/2025

Thrilled to see my #MITS25 talk brought to life by the brilliant 🎨 @atjcagan.bsky.social! Dive into the stellar science from @g-agarwal.bsky.social & co - fresh on bioRxiv: www.biorxiv.org/content/10.1... #Genomics #SomaticEvolution

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Tim Coorens @timcoorens.bsky.social · 27/04/2025

Thanks again for coming over to speak! It was an amazing talk

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Thanks to all the donors and their families for making this study possible. And many thanks to Grace Collord, Peter Campbell, @imartincorena.bsky.social , SY Leung, Mike Stratton and all other co-authors. @broadinstitute.org @sangerinstitute.bsky.social

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In short, the normal stomach shows a landscape of somatic mutations with many differences from those of other organs. Our findings provide insights into intrinsic and extrinsic influences on somatic evolution in the gastric epithelium in healthy, precancerous and malignant states

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Because we used the LCM approach, we can map these driver clones to their location in tissues, which reveals expansions of mutant clones and local selective pressures. We find three CTNNB1 mutant clones right next to one another, rather than evenly distributed.

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Lastly, the stomach also shows a rich landscape of driver mutations, most notably in epigenetic modifiers (ARID1A, ARID1B, KDM6A) and surprisingly inactivating mutations in CTNNB1 (unlike the activating ones observed in cancer).

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Glands with trisomies were not associated with a specific stomach region, and their incidence does not linearly increase with age, but are associated with severe chronic inflammation. It's plausible these are a consequence of an exposure, a pathogen or otherwise, long before the time of sampling.

Intriguingly, these trisomies happen multiple times in the same donor, with different alleles amplified. In one case, we found trisomies in 9 of 12 glands sampled. Timing analysis shows these all happened around the same time, suggesting a sudden burst or selective advantage.

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The most surprising finding, however, comes from the CNVs in the stomach. We find extraordinarily high rates of somatic whole-chromosome gains/trisomies in the stomach, mostly of chrs 20 and 13, highly concentrated in a few patients.

While SBS17 is very common in gastric cancer, we only find it very rarely in normal glands, and only in very low proportions. So while stomach cells can get exposed to SBS17, high levels of SBS17 seem to be exclusive to overt cancer.

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The mutational signatures are mostly SBS1, SBS5 and SBS18, like other epithelial tissues. Metaplastic glands have much more SBS1 and SBS18 (ROS), and indels linked to polymerase slippage. These are also dominant in intestinal glands, so may suggest a “rewiring” of the mutation rate.

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These hypermutant glands are almost exclusively in the antrum of the stomach, chronically inflamed and most importantly, metaplastic. Intestinal metaplasia is a well-known precursor to gastric cancer, but these aren't monoclonal expansions.

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We find that gastric glands are clonal units arising from a single stem cell. In non-cancer donors, the mutation rate is 28 SNVs and 2 indels per year. This is mostly true in cancer patients, but some patients have many "hypermutant" glands, with far more mutations than expected.

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The lining of the stomach produces acid, and is the origin of stomach cancer, with many risk factors (diet, smoking, H. pylori infection). We used LCM to isolate and sequence normal stomach glands, from gastric cancer patients and non-cancer donors, from Hong Kong, the US and UK.

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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...

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Reposted by Tim Coorens

Martin Smith @martinalexsmith.bsky.social · 24/02/2025

@timcoorens.bsky.social diving into the Bostonian wing of the SMaHT program (a.k.a. 'wicked SMaHT), detailing new sequencing solution for ultra high accuracy duplex sequencing, essential for detecting somatic variation #AGBTgm

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Reposted by Tim Coorens

Mike Schatz @mikeschatz.bsky.social · 24/02/2025

Awesome talk by @timcoorens.bsky.social on the detection and interpretation of somatic mutations. Now hiring postdocs! #AGBT25 | #AGBTGM

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This effort is made possible by the funders, co-authors, and a large group of passionate and amazing scientists across many institutes! Most importantly, this work would not be possible without the generosity of the donations. @broadinstitute.org @yaleschoolofmed.bsky.social @ohsunews.bsky.social

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The Genotype-Tissue Expression (GTEx) project is an ongoing effort to build a comprehensive public resource to study tissue-specific gene expression and regulation. Samples were collected from 53 non-...

GTEx (v10 just released!) was a massive-scale effort to generate gene expression and molecular profiles across dozens of human tissues from ~1,000 donors, spurring research into tissue-specific expression, QTLs and much more. gtexportal.org will include dGTEx when released.

gtexportal.org

GTEx Portal

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Beyond being a reference dataset for normal human and NHP development, dGTEx will enable research into developmental and childhood disorders, the effect of genetic variation during development, genetic causes of developmental disorders, and translational therapeutics.

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There is great unmet need for this data. Children are not simply tiny adults and are critically underrepresented in studies, many relying on adult tissues. In parallel, little is known about development across non-human primates, with implications for human evolution and comparative medicine.

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The dGTEx project extends GTEx across development and across species. We are currently collecting tissues from pediatric donors, marmosets and macaques to generate whole genome, transcriptomic and chromatin profiles to study developmental variation in gene expression and regulation.

Our new perspective article describing the human and non-human primate developmental GTEx projects is now out in @nature.com! We outline the scope, vision, opportunities and challenges of these projects here: www.nature.com/articles/s41...