Nuria Lopez-Bigas
@nlbigas.bsky.social
ICREA Research Professor at IRB Barcelona. Working on computational cancer genomics. Leading @bbglab.bsky.social
http://bbglab.irbbarcelona.org
http://bbglab.irbbarcelona.org
Hotspots of human mutation point to clonal expansions in spermatogonia
by @vseplyarskiy.bsky.social, Shamil Sunyaev et al
www.nature.com/articles/s41...
by @vseplyarskiy.bsky.social, Shamil Sunyaev et al
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.
www.nature.com
October 8, 2025 at 4:56 PM
Hotspots of human mutation point to clonal expansions in spermatogonia
by @vseplyarskiy.bsky.social, Shamil Sunyaev et al
www.nature.com/articles/s41...
by @vseplyarskiy.bsky.social, Shamil Sunyaev et al
www.nature.com/articles/s41...
Sperm sequencing reveals extensive positive selection in the male germline
By @r-rahbari.bsky.social et al
www.nature.com/articles/s41...
By @r-rahbari.bsky.social 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.
www.nature.com
October 8, 2025 at 4:56 PM
Sperm sequencing reveals extensive positive selection in the male germline
By @r-rahbari.bsky.social et al
www.nature.com/articles/s41...
By @r-rahbari.bsky.social et al
www.nature.com/articles/s41...
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...
Somatic mutation and selection at population scale
By @imartincorena.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.
www.nature.com
October 8, 2025 at 4:56 PM
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...
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.
October 8, 2025 at 4:44 PM
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.
October 8, 2025 at 4:44 PM
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.
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.
In silico saturation mutagenesis of cancer genes - Nature
A new computational approach to in silico mutagenesis screening allow comprehensive mapping of cancer driver mutations.
www.nature.com
October 8, 2025 at 4:44 PM
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.
October 8, 2025 at 4:44 PM
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.
October 8, 2025 at 4:44 PM
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.
October 8, 2025 at 4:44 PM
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
➡️ Truncating mutations in FGFR3 are under negative selection
➡️ Activating mutations in the TERT promoter are under strong positive selection in normal bladder
October 8, 2025 at 4:44 PM
➡️ 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
➡️ 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
Each tumor is a clone, but in normal tissue, with this approach we can detect mutations in hundreds of clones in each sample
October 8, 2025 at 4:44 PM
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
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
➡️ We identified somatic mutations in 16 genes (around 5,000x) using ultra-deep error-corrected duplex sequencing
➡️ We studied clonal diversity across individuals
October 8, 2025 at 4:44 PM
➡️ 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
➡️ 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.
October 8, 2025 at 4:44 PM
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.
congratulations to all the team 👏
October 5, 2025 at 6:40 PM
congratulations to all the team 👏