Benjamin Schuster-Böckler
@dagams.bsky.social
Group leader at the Ludwig Institute for Cancer Research in Oxford. Computational genomics and bioinformatics.
Also find me on genomic.social, a free and non-profit Mastodon instance for genomics (@bensb@genomic.social)
Also find me on genomic.social, a free and non-profit Mastodon instance for genomics (@bensb@genomic.social)
Interesting preprint, but - respectfully - I think several conclusions drawn from the data are exaggerated. E.g. this figure. The fit of this curve is terrible. A ⍴ of 0.023 isn't impressive. Not sure I'd agree this proves that DREAM levels predict lifespan across species.
September 29, 2025 at 12:15 PM
Interesting preprint, but - respectfully - I think several conclusions drawn from the data are exaggerated. E.g. this figure. The fit of this curve is terrible. A ⍴ of 0.023 isn't impressive. Not sure I'd agree this proves that DREAM levels predict lifespan across species.
I canz do great stats, too 😅
February 16, 2025 at 6:52 AM
I canz do great stats, too 😅
Happy holidays from the BSB lab 🎄🥳
December 17, 2024 at 4:31 PM
Happy holidays from the BSB lab 🎄🥳
By either methylating or not methylating the ROI, we can then test if Pol-ε makes more errors when copying methyl-C than C.
If you've read this far, the big reveal is not going to be too surprising: Pol-ε, even with proofreading intact, often puts an A opposite methyl-C!
13/🧵
If you've read this far, the big reveal is not going to be too surprising: Pol-ε, even with proofreading intact, often puts an A opposite methyl-C!
13/🧵
December 2, 2024 at 12:12 PM
By either methylating or not methylating the ROI, we can then test if Pol-ε makes more errors when copying methyl-C than C.
If you've read this far, the big reveal is not going to be too surprising: Pol-ε, even with proofreading intact, often puts an A opposite methyl-C!
13/🧵
If you've read this far, the big reveal is not going to be too surprising: Pol-ε, even with proofreading intact, often puts an A opposite methyl-C!
13/🧵
Through a combination of cleanup steps, double-barcoding of single molecules and a lot of clever computational filtering, we are able to detect replication errors in single molecules!
12/🧵
12/🧵
December 2, 2024 at 12:12 PM
Through a combination of cleanup steps, double-barcoding of single molecules and a lot of clever computational filtering, we are able to detect replication errors in single molecules!
12/🧵
12/🧵
After many analyses and scratching of heads, we proposed that maybe DNA replication is itself mutagenic by occasionally mis-reading methyl-C as T, putting an A opposite it. Normally this is repaired by proofreading or MMR, but in their absence you get a massive increase in mutations!
8/🧵
8/🧵
December 2, 2024 at 12:12 PM
After many analyses and scratching of heads, we proposed that maybe DNA replication is itself mutagenic by occasionally mis-reading methyl-C as T, putting an A opposite it. Normally this is repaired by proofreading or MMR, but in their absence you get a massive increase in mutations!
8/🧵
8/🧵
It turns out that the opposite is the case! MMR deficient cancers have more C>T mutations at CpG. Cancers that loose proofreading of the main replicative polymerase (Pol-ε) have an even higher rate of C>T at CpG. So how can this be?
7/🧵
7/🧵
December 2, 2024 at 12:12 PM
It turns out that the opposite is the case! MMR deficient cancers have more C>T mutations at CpG. Cancers that loose proofreading of the main replicative polymerase (Pol-ε) have an even higher rate of C>T at CpG. So how can this be?
7/🧵
7/🧵
C>T mutations at CpG are not just common in the germline, they are also the most common mutation type across cancer. The COSMIC database of unique "mutational signatures" in cancer calls them Signature 1, and shows how ubiquitous this process really is!
4/🧵
4/🧵
December 2, 2024 at 12:12 PM
C>T mutations at CpG are not just common in the germline, they are also the most common mutation type across cancer. The COSMIC database of unique "mutational signatures" in cancer calls them Signature 1, and shows how ubiquitous this process really is!
4/🧵
4/🧵
This was attributed to a simple chemical reaction: "spontaneous deamination" of mC, producing T. This is incompletely repaired by base-excision repair. For decades, this has been the standard explanation for the high frequency of C>T mutations at methyl-cytosine (figure from bit.ly/4eVJfzE)
3/🧵
3/🧵
December 2, 2024 at 12:12 PM
This was attributed to a simple chemical reaction: "spontaneous deamination" of mC, producing T. This is incompletely repaired by base-excision repair. For decades, this has been the standard explanation for the high frequency of C>T mutations at methyl-cytosine (figure from bit.ly/4eVJfzE)
3/🧵
3/🧵
Methylation at CpG dinucleotides C is an important epigenetic modification. It was noticed more than 40 years ago that in many mammalian genomes, there’s less CpG and more TpG than you’d expect by chance (in a classic paper from Adrian Bird: academic.oup.com/nar/article-...)
2/🧵
2/🧵
December 2, 2024 at 12:12 PM
Methylation at CpG dinucleotides C is an important epigenetic modification. It was noticed more than 40 years ago that in many mammalian genomes, there’s less CpG and more TpG than you’d expect by chance (in a classic paper from Adrian Bird: academic.oup.com/nar/article-...)
2/🧵
2/🧵