Natanael Spisak
@natanaels.bsky.social
I study how mutations come about. Based at @columbiauniversity.bsky.social, previously at @normalesup.bsky.social
Pinned
In these dark times, it comes as a rare pleasure to highlight @natanaels.bsky.social & @marcdemanuel.bsky.social's work on germline and somatic mutations in humans. 1/n
www.biorxiv.org/cgi/content/...
www.biorxiv.org/cgi/content/...
Collateral mutagenesis funnels multiple sources of DNA damage into a ubiquitous mutational signature
Mutations reflect the net effects of myriad types of damage, replication errors, and repair mechanisms, and thus are expected to differ across cell types with distinct exposures to mutagens, division ...
www.biorxiv.org
Very happy to share our work on signature SBS5. See Molly's thread for a short summary
Reposted by Natanael Spisak
Excited to share a preprint of my PhD project looking at interactions between SNPs and polygenic scores in the UK Biobank!
A thread... 🧵
www.medrxiv.org/content/10.1...
A thread... 🧵
www.medrxiv.org/content/10.1...
Interactions with polygenic background impact quantitative traits in the UK Biobank
Association studies have linked many genetic variants to a variety of phenotypes but under-standing the biological mechanisms underlying these signals remains a major challenge. Since genes operate wi...
www.medrxiv.org
November 24, 2025 at 5:13 PM
Excited to share a preprint of my PhD project looking at interactions between SNPs and polygenic scores in the UK Biobank!
A thread... 🧵
www.medrxiv.org/content/10.1...
A thread... 🧵
www.medrxiv.org/content/10.1...
Reposted by Natanael Spisak
Super cool paper from Sheel Chandra + Ziyue Gao. kmer context matters a lot for mutability of both methylated and unmethylated CpGs.
But!! the effect of kmer context on unmethylated CpGs is basically independent of the effect of kmer context on methylated CpGs!
www.biorxiv.org/content/10.1...
But!! the effect of kmer context on unmethylated CpGs is basically independent of the effect of kmer context on methylated CpGs!
www.biorxiv.org/content/10.1...
Sequence context and methylation interact to shape germline mutation rate variation at CpG sites
A prominent example of sequence context-dependent mutation rate variation is the elevated transition rate at CpG sites, which is largely attributed to cytosine methylation. CpGs with different flankin...
www.biorxiv.org
November 18, 2025 at 8:13 PM
Super cool paper from Sheel Chandra + Ziyue Gao. kmer context matters a lot for mutability of both methylated and unmethylated CpGs.
But!! the effect of kmer context on unmethylated CpGs is basically independent of the effect of kmer context on methylated CpGs!
www.biorxiv.org/content/10.1...
But!! the effect of kmer context on unmethylated CpGs is basically independent of the effect of kmer context on methylated CpGs!
www.biorxiv.org/content/10.1...
Reposted by Natanael Spisak
SAVE THE DATE: the yearly NY Population Genetics meeting will be back on March 9 2026, generously hosted by the
@simonsfoundation.org. Details to follow. Please RT.
@simonsfoundation.org. Details to follow. Please RT.
November 14, 2025 at 5:05 PM
SAVE THE DATE: the yearly NY Population Genetics meeting will be back on March 9 2026, generously hosted by the
@simonsfoundation.org. Details to follow. Please RT.
@simonsfoundation.org. Details to follow. Please RT.
Reposted by Natanael Spisak
The exciting next instalment of Mutations in Time and Space... Open for registration now
Explore the origins, patterns and consequences of mutations across biological systems! #MITS26
🗓️ Conference dates: 13-15 April 2026
Participate in expert-led knowledge exchange on how genome evolution shapes human health and ageing 🧬
Check out our exciting speakers ➡️ bit.ly/4hmbnyr
#Genomics
🗓️ Conference dates: 13-15 April 2026
Participate in expert-led knowledge exchange on how genome evolution shapes human health and ageing 🧬
Check out our exciting speakers ➡️ bit.ly/4hmbnyr
#Genomics
November 4, 2025 at 10:28 AM
The exciting next instalment of Mutations in Time and Space... Open for registration now
Reposted by Natanael Spisak
A helpful visual in many ways
Scoop: Trump has started demolishing the White House's East Wing facade to build his ballroom. The president had claimed construction of the $250 million building wouldn’t ‘interfere’ with the existing White House structure. /W @ddiamond.bsky.social wapo.st/4hqBNiU
White House begins demolishing East Wing facade to build Trump’s ballroom
The president had claimed construction of the $250 million ballroom wouldn’t ‘interfere’ with the existing White House structure.
wapo.st
October 20, 2025 at 7:26 PM
A helpful visual in many ways
Reposted by Natanael Spisak
Mutations in Time and Space is headed to Cambridge, UK for 2026!
You can check out the exciting list of invited speakers here: coursesandconferences.wellcomeconnectingscience.org/event/mutati...
See you at the Wellcome Genome Campus, on 13–15 April?
Nice one! ;-) #MITS26
You can check out the exciting list of invited speakers here: coursesandconferences.wellcomeconnectingscience.org/event/mutati...
See you at the Wellcome Genome Campus, on 13–15 April?
Nice one! ;-) #MITS26
Mutations in Time and Space — 20260413
Mutations in Time and Space
coursesandconferences.wellcomeconnectingscience.org
October 13, 2025 at 10:07 AM
Mutations in Time and Space is headed to Cambridge, UK for 2026!
You can check out the exciting list of invited speakers here: coursesandconferences.wellcomeconnectingscience.org/event/mutati...
See you at the Wellcome Genome Campus, on 13–15 April?
Nice one! ;-) #MITS26
You can check out the exciting list of invited speakers here: coursesandconferences.wellcomeconnectingscience.org/event/mutati...
See you at the Wellcome Genome Campus, on 13–15 April?
Nice one! ;-) #MITS26
Reposted by Natanael Spisak
Mutation bias in driver genes reveals the distribution of effects of oncogenic mutations https://www.biorxiv.org/content/10.1101/2025.09.25.678277v1
September 29, 2025 at 3:32 AM
Mutation bias in driver genes reveals the distribution of effects of oncogenic mutations https://www.biorxiv.org/content/10.1101/2025.09.25.678277v1
Reposted by Natanael Spisak
Studying cancer evolution needs multi-region or single cell seq for phylogenetics, right? Amazingly (I think!) we found single-sample bulk methylation suffices, via analysis of "fluctuating methylation". In @nature.com today led by brilliant @calumgabbutt.bsky.social www.nature.com/articles/s41...
Fluctuating DNA methylation tracks cancer evolution at clinical scale - Nature
Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.
www.nature.com
September 10, 2025 at 3:21 PM
Studying cancer evolution needs multi-region or single cell seq for phylogenetics, right? Amazingly (I think!) we found single-sample bulk methylation suffices, via analysis of "fluctuating methylation". In @nature.com today led by brilliant @calumgabbutt.bsky.social www.nature.com/articles/s41...
Very happy to share our work on signature SBS5. See Molly's thread for a short summary
In these dark times, it comes as a rare pleasure to highlight @natanaels.bsky.social & @marcdemanuel.bsky.social's work on germline and somatic mutations in humans. 1/n
www.biorxiv.org/cgi/content/...
www.biorxiv.org/cgi/content/...
Collateral mutagenesis funnels multiple sources of DNA damage into a ubiquitous mutational signature
Mutations reflect the net effects of myriad types of damage, replication errors, and repair mechanisms, and thus are expected to differ across cell types with distinct exposures to mutagens, division ...
www.biorxiv.org
September 3, 2025 at 3:56 PM
Very happy to share our work on signature SBS5. See Molly's thread for a short summary
Reposted by Natanael Spisak
Would you like to do some unique experiments in cancer genomics and mutagenesis, in beautiful Munich? Well then apply for this PhD position: jobs.dkfz.de/en/jobs/1679...
You'll learn a lot and it'll be fun and interesting!
#DKTK @dkfz.bsky.social @lmumuenchen.bsky.social
You'll learn a lot and it'll be fun and interesting!
#DKTK @dkfz.bsky.social @lmumuenchen.bsky.social
PhD Student in Mutational Processes Driving Somatic Evolution
jobs.dkfz.de
August 19, 2025 at 2:54 PM
Would you like to do some unique experiments in cancer genomics and mutagenesis, in beautiful Munich? Well then apply for this PhD position: jobs.dkfz.de/en/jobs/1679...
You'll learn a lot and it'll be fun and interesting!
#DKTK @dkfz.bsky.social @lmumuenchen.bsky.social
You'll learn a lot and it'll be fun and interesting!
#DKTK @dkfz.bsky.social @lmumuenchen.bsky.social
Reposted by Natanael Spisak
I'm thrilled that my lab at NYU is now supported by an NIH MIRA grant! I'm looking to hire 1-2 senior lab members (outstanding postdoc candidates or experienced staff scientists) with expertise in computational or statistical methods in human genetics or genomics. Please share!
July 25, 2025 at 8:29 PM
I'm thrilled that my lab at NYU is now supported by an NIH MIRA grant! I'm looking to hire 1-2 senior lab members (outstanding postdoc candidates or experienced staff scientists) with expertise in computational or statistical methods in human genetics or genomics. Please share!
Reposted by Natanael Spisak
Those who enjoyed the plenary talk from @mollyprz.bsky.social this morning at #SMBE2025 might like to read more about this work in this 2024 @plosbiology.org paper with @natanaels.bsky.social &co: journals.plos.org/plosbiology/...
The clock-like accumulation of germline and somatic mutations can arise from the interplay of DNA damage and repair
The rate at which DNA mutations accumulate varies substantially across cell types and tissues in the human body, but the origin of these differences is not well understood. This study develops a model...
journals.plos.org
July 22, 2025 at 2:42 AM
Those who enjoyed the plenary talk from @mollyprz.bsky.social this morning at #SMBE2025 might like to read more about this work in this 2024 @plosbiology.org paper with @natanaels.bsky.social &co: journals.plos.org/plosbiology/...
Reposted by Natanael Spisak
It was fun writing this short piece on the omnigenic model. Sharing it here, though it's a painful time as my family, along with millions of others, is at risk in Iran and the region.
New online! Making sense of the polygenicity of complex traits
Making sense of the polygenicity of complex traits
Nature Reviews Genetics, Published online: 16 June 2025; doi:10.1038/s41576-025-00866-7Hakhamanesh Mostafavi recalls a landmark paper by Boyle et al. on the omnigenic model, which proposed that complex traits are influenced by thousands of genes across the genome, including many that are only indirectly related to a trait through regulatory networks.
www.nature.com
June 17, 2025 at 3:15 PM
It was fun writing this short piece on the omnigenic model. Sharing it here, though it's a painful time as my family, along with millions of others, is at risk in Iran and the region.
Reposted by Natanael Spisak
Please check out our new approach to modeling somatic mutation signatures.
DAMUTA has independent Damage and Misrepair signatures whose activities are more interpretable and more predictive of DNA repair defects, than COSMIC SBS signatures 🧬🖥️🧪
www.biorxiv.org/content/10.1...
DAMUTA has independent Damage and Misrepair signatures whose activities are more interpretable and more predictive of DNA repair defects, than COSMIC SBS signatures 🧬🖥️🧪
www.biorxiv.org/content/10.1...
Damage and Misrepair Signatures: Compact Representations of Pan-cancer Mutational Processes
Mutational signatures of single-base substitutions (SBSs) characterize somatic mutation processes which contribute to cancer development and progression. However, current mutational signatures do not ...
www.biorxiv.org
June 3, 2025 at 12:34 AM
Please check out our new approach to modeling somatic mutation signatures.
DAMUTA has independent Damage and Misrepair signatures whose activities are more interpretable and more predictive of DNA repair defects, than COSMIC SBS signatures 🧬🖥️🧪
www.biorxiv.org/content/10.1...
DAMUTA has independent Damage and Misrepair signatures whose activities are more interpretable and more predictive of DNA repair defects, than COSMIC SBS signatures 🧬🖥️🧪
www.biorxiv.org/content/10.1...
Reposted by Natanael Spisak
Elegant new theory on polygenic adaptation by Will Milligan, Laura Heyward, and Guy Sella.
When should adaptation arise from a polygenic response versus few large effect changes? https://www.biorxiv.org/content/10.1101/2025.05.15.654234v1
May 17, 2025 at 11:55 PM
Elegant new theory on polygenic adaptation by Will Milligan, Laura Heyward, and Guy Sella.
Reposted by Natanael Spisak
Reposted by Natanael Spisak
My lab at hiring! - we have TWO postdoc positions (one computational, one wet lab focussed) at Yale @yaleschoolofmed.bsky.social, working closely with our group members at University of Cambridge, UK @cambridgeuni.bsky.social
Please help to spread the word!
Adverts with full details below ⬇️
Please help to spread the word!
Adverts with full details below ⬇️
March 26, 2025 at 3:31 PM
My lab at hiring! - we have TWO postdoc positions (one computational, one wet lab focussed) at Yale @yaleschoolofmed.bsky.social, working closely with our group members at University of Cambridge, UK @cambridgeuni.bsky.social
Please help to spread the word!
Adverts with full details below ⬇️
Please help to spread the word!
Adverts with full details below ⬇️
Reposted by Natanael Spisak
📣 Two ERC-funded positions are available in the lab! If you are interested in exploring the mechanisms underlying mutation, we’d love to hear from you.
PhD: shorturl.at/Oc04N
Postdoc: shorturl.at/1ShHB
RPs and shares would be greatly appreciated!
🧪🧬🖥️ #ScienceJobs #PostdocJobs
PhD: shorturl.at/Oc04N
Postdoc: shorturl.at/1ShHB
RPs and shares would be greatly appreciated!
🧪🧬🖥️ #ScienceJobs #PostdocJobs
November 25, 2024 at 11:19 AM
📣 Two ERC-funded positions are available in the lab! If you are interested in exploring the mechanisms underlying mutation, we’d love to hear from you.
PhD: shorturl.at/Oc04N
Postdoc: shorturl.at/1ShHB
RPs and shares would be greatly appreciated!
🧪🧬🖥️ #ScienceJobs #PostdocJobs
PhD: shorturl.at/Oc04N
Postdoc: shorturl.at/1ShHB
RPs and shares would be greatly appreciated!
🧪🧬🖥️ #ScienceJobs #PostdocJobs
Reposted by Natanael Spisak
UCSF hosted its first food pantry event for postdocs today, where a local food bank gives free food to UCSF employees.
This picture represents about half the line that had formed 10 minutes before the market had opened.
What the fuck are we doing here guys?
This picture represents about half the line that had formed 10 minutes before the market had opened.
What the fuck are we doing here guys?
November 21, 2024 at 2:04 AM
UCSF hosted its first food pantry event for postdocs today, where a local food bank gives free food to UCSF employees.
This picture represents about half the line that had formed 10 minutes before the market had opened.
What the fuck are we doing here guys?
This picture represents about half the line that had formed 10 minutes before the market had opened.
What the fuck are we doing here guys?
Reposted by Natanael Spisak
Do people know about the STEM Jobs feed? Seems useful to put related job postings together in one place. #ScienceJobs
November 12, 2024 at 6:33 PM
Do people know about the STEM Jobs feed? Seems useful to put related job postings together in one place. #ScienceJobs
Reposted by Natanael Spisak
1/ A thread about mutation and recombination in vertebrates and what we learned by studying three-generation pedigrees of zebra finches. Take home: the remarkable similarities between birds and mammals in many properties of these fundamental processes.
Conservation of mutation and recombination parameters between mammals and zebra finch https://www.biorxiv.org/content/10.1101/2024.09.05.611523v1
Conservation of mutation and recombination parameters between mammals and zebra finch https://www.biorxiv.org/content/10.1101/2024.09.05.611523v1
Most of our understanding of the fundamental processes of mutation and recombination stems from a ha
www.biorxiv.org
September 6, 2024 at 3:17 PM
1/ A thread about mutation and recombination in vertebrates and what we learned by studying three-generation pedigrees of zebra finches. Take home: the remarkable similarities between birds and mammals in many properties of these fundamental processes.
Reposted by Natanael Spisak
@natanaels.bsky.social's work modeling how mutations accumulate with age and time, now out in PLoS Biology (joint with @marcdemanuel.bsky.social, William Milligan & Guy Sella): journals.plos.org/plosbiology/...
The clock-like accumulation of germline and somatic mutations can arise from the interplay of DNA damage and repair
The rate at which DNA mutations accumulate varies substantially across cell types and tissues in the human body, but the origin of these differences is not well understood. This study develops a model...
journals.plos.org
June 18, 2024 at 12:57 PM
@natanaels.bsky.social's work modeling how mutations accumulate with age and time, now out in PLoS Biology (joint with @marcdemanuel.bsky.social, William Milligan & Guy Sella): journals.plos.org/plosbiology/...
Reposted by Natanael Spisak
Come join us in the Zuckerman Institute at Columbia on May 17th for the 2024 New York Area Population Genetics Meeting.
Keynotes by Lindy McBraide and Cedric Feschotte
Register here zuckermaninstitute.columbia.edu/new-york-are...
Keynotes by Lindy McBraide and Cedric Feschotte
Register here zuckermaninstitute.columbia.edu/new-york-are...
NYAPG24
Join us on Friday, May 17, 2024 for an all-day conference hosted at Columbia’s Zuckerman Institute showcasing research in evolutionary genetics. Alongside formal presentations, the conference will enc...
zuckermaninstitute.columbia.edu
February 9, 2024 at 5:04 PM
Come join us in the Zuckerman Institute at Columbia on May 17th for the 2024 New York Area Population Genetics Meeting.
Keynotes by Lindy McBraide and Cedric Feschotte
Register here zuckermaninstitute.columbia.edu/new-york-are...
Keynotes by Lindy McBraide and Cedric Feschotte
Register here zuckermaninstitute.columbia.edu/new-york-are...