Nuria Lopez-Bigas

📢 This Week at #IRBBarcelona: Join us for a plenary #seminar this Friday, with Dr. @isidrolauscher.bsky.social from @ebi.embl.org @sangerinstitute.bsky.social @cancerresearchuk.org 

🤝 Hosted by @nlbigas.bsky.social and @milanlab.bsky.social 

Register here ➡️ https://shorturl.at/imwHx

🧪

#internationaldayofwomenandgirlsinscience #eacr #womeninscience | Johanna Joyce Today is the #InternationalDayofWomenandGirlsinScience - a moment to recognise and celebrate women across all of the #EACR community 🙌 From Board members working together across Europe, to the dedic...

Today is the #InternationalDayofWomenandGirlsinScience - celebrating women across our @helloeacr.bsky.social community 🙌

From Board members across Europe to the #EACR HQ team and the scientists we serve worldwide, women play a central role in advancing cancer research every day

#WomeninScience 👩🏻‍🔬🧪

This week, Loic Verlingue (CLB) & Santi Demajo (@irbbarcelona.org) represented CGI-Clinics at the EUnetCCC seminar 'Advancing Precision Oncology through Molecular Tumour Boards' - a fantastic opportunity to bring the CGI tool to the forefront of the European precision cancer diagnostics community 🌍

Huge congratulations to Fran on being awarded the ERC Consolidator Grant! 🎉

Such a well-deserved recognition of an outstanding trajectory and a truly creative, exciting proposal on T-cell clonal hematopoiesis.

Can’t wait to see the discoveries that come out of this project.

So proud of you! 👏✨

Today, Nuria López-Bigas @nlbigas.bsky.social and Mònica Sánchez-Guixé @guixe-m.bsky.social are at the #BarcelonaBiomed Conference, organised by #IRBBarcelona.
A great occasion to share our projects related to childhood cancers.

Delighted and honored to have hosted the 3rd PROMINENT Retreat in Barcelona.
The @cancergrand.bsky.social project led by Allan Balmain, Paul Brennan and Nuria Lopez-Bigas, is progressing thanks to the excellent science being performed by all the teams. Great meeting and best participants!

Don't miss our extraordinary #seminar to be held next week, with @jdegregori.bsky.social, from the University of Colorado Anschutz (@cuanschutz.bsky.social).

Host: Dr. @nlbigas.bsky.social (@bbglab.bsky.social, #IRBBarcelona)

Register here 👉 https://shorturl.at/n74Th

#CancerResearch

🧪

Excited to see this thought provoking piece of work now published. So much more to learn about mutagenesis in healthy tissue.

Very excited to share our new paper on the influence of biological sex and smoking in the clonal landscape of normal human bladder, just published in Nature.
A big thank you and congrats to all the authors, specially to @raquelbmi.bsky.social for all the shared efforts in this journey!

⬇️More info⬇️

Very happy to share that our paper on the influence of biological sex and smoking in the clonal landscape of the normal human bladder is out today in Nature. Kudos to all the authors and especially to @ferriol.bsky.social for coming along with me during this project's journey!

🧵Summary following ⬇️

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...

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.

Sperm sequencing reveals extensive positive selection in the male germline

By @r-rahbari.bsky.social et al

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.

Check also other very interesting papers published in the same issue 👇

Somatic mutation and selection at population scale

By @imartincorena.bsky.social et al

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

This was only possible thanks to the work of many people and countless discussions, but especially thanks to the generosity of the donors and their families.

With the large number of mutations detected with duplex sequencing in normal tissue, we are approaching Natural Saturation Mutagenesis. And this allows us to compute positive selection at subgenic resolution, even per residue.

In silico saturation mutagenesis of cancer genes - Nature A new computational approach to in silico mutagenesis screening allow comprehensive mapping of cancer driver mutations.

Few years ago we published a paper titled “In silico saturation mutagenesis of cancer genes” www.nature.com/articles/s41... in which we used mutations in thousands of tumors to build machine learning models that can identify all driver mutations in cancer genes.

We also found a significantly increased number of TERT promoter activating mutations among smokers (ex- and current) above 55 years old.

Part of this variability is due to differences in selection between males and females, specifically on truncating mutations in RBM10, ARID1A and CDKN1A, which appear to provide stronger advantage to urothelium cells in males.

The unprecedented number of mutations per gene per sample together with the development of new analysis tools allowed us to compute the magnitude of positive selection on the mutations of each gene in each sample. This revealed a landscape of extensive interindividual variability in the cohort.

➡️ Most genes in the panel show strong signals of positive selection
➡️ Truncating mutations in FGFR3 are under negative selection
➡️ Activating mutations in the TERT promoter are under strong positive selection in normal bladder

With this approach we find thousands of somatic mutations in the normal urothelium of 45 individuals, many more than those seen in bladder tumors sequenced over two decades

Each tumor is a clone, but in normal tissue, with this approach we can detect mutations in hundreds of clones in each sample

➡️ We collected cytobrush samples from the top and the bottom of the bladder urothelium of 45 individuals during autopsy

➡️ We identified somatic mutations in 16 genes (around 5,000x) using ultra-deep error-corrected duplex sequencing

➡️ We studied clonal diversity across individuals

Human somatic tissues evolve as mosaics of competing clones driven by mutations. Most of these clones do not result in cancer, but some of them can constitute the first steps of the trajectory towards a malignant tumor. What influences this evolution in each tissue remains unknown.

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)

congratulations to all the team 👏

Oncodrive3D: fast and accurate detection of structural clusters of somatic mutations under positive selection Abstract. Identifying the genes capable of driving tumorigenesis in different tissues is one of the central goals of cancer genomics. Computational methods

New paper from our lab - ‪@bbglab.bsky.social‬.

Oncodrive3D: fast and accurate detection of structural clusters of somatic mutations under positive selection

academic.oup.com/nar/article/...

Kudos to Stefano, Olivia, @fmuinos.bsky.social and Abel

Back after a few days in Lisbon for the annual #EACR2025 conference! Inspiring and great science. Glad for the opportunity to present our work, coming home with a bunch of new ideas! @bbglab.bsky.social @ferriol.bsky.social

@ewaszczurek.bsky.social explains how evolution is the generative process of cancer at #AACR25.

Jeffrey Townsend (that's me!) presents on dismantling the coarse approximation of drivers and passengers in cancer at #AACR25.

Thank you @nlbigas.bsky.social for the photo!

@nlbigas.bsky.social explains how they assemble a compenduim of driver genes 🧬 in cancer at #AACR25.