Natanael Spisak
@natanaels.bsky.social
Building a new lab at @institutimagine.bsky.social; previously at @columbiauniversity.bsky.social @normalesup.bsky.social 🔗 https://natanaelspisak.github.io
You can now register for Mutations in time and space 2027 🎉🎉🎉🎉🎉🎉 www.embl.org/about/info/c... 🎉🎉🎉🎉🎉🎉 This time we're in beautiful Heidelberg over 15 - 18 June. Along with a stellar cast of invited speakers, there are a ton of slots for submitted abstracts. Please do come along and take part :-)
Mutations in time and space
embl.org
Excited to see @jonj-udd.bsky.social's fantastic work out @genetics-gsa.bsky.social. Selection in _heterozygotes_ is the primary force shaping allele frequencies of loss-of-function mutations in humans, even in genes only associated with purely recessive diseases. 🧪🧬 doi.org/10.1093/gene...
Allele Frequencies at Recessive Disease Genes are Mainly Determined by Pleiotropic Effects in Heterozygotes
Abstract. The classic theory of mutation-selection balance predicts the equilibrium frequency of genetic variation under negative selection. The model pred
doi.org
Please help me find a great student! I have a PhD position in my lab in Munich, looking at the dynamics of DNA damage and repair from chemotherapy: jobs.dkfz.de/en/jobs/1686... The application deadline is 02.07.26 @dkfz.bsky.social @lmu-klinikum.bsky.social
PhD Student in Mutagenic Chemotherapy Driving Treatment Resistance
jobs.dkfz.de
Interested in DNA damage and the mechanisms of mutagenesis? We are hiring post-doctoral scientists as part of the amazing CAUSE Cancer Grand Challenge team. Biochemistry, genomics and computational biology... tinyurl.com/yc5xs3wa tinyurl.com/4unu5uu9 CAUSE www.cancergrandchallenges.org/cause
I am delighted to share new work with Simon Myers (www.biorxiv.org/content/10.6...), on how genetic variants that influence binding patterns of PRDM9 and slow down the repair of meiotic double-strand breaks impact mammalian spermatogenesis and fertility. 1/n
biorxiv.org
Happy to highlight new findings by Vanesa Getseva and Lin Poyraz about the sources of variation in germline mutation rates among humans: www.biorxiv.org/content/10.6... Joint work with Anastasia Stolyarova and @ipsitaagarwal.bsky.social. 1/n
A sibling study of variation in parental mutation rates
People are born with variable numbers of de novo germline mutations (DNMs), depending primarily on the ages of their parents. To explore additional causes, we developed an approach to call DNMs from nucleotide differences between siblings in genomic regions inherited identical by descent from both parents. Applying it to whole genome sequences from 28,985 sibling pairs of diverse genetic ancestries present in the UK Biobank and All of Us datasets, as well as 2,330 trios, we identified >800K autosomal DNMs and characterized mutation phenotypes in 27,645 sets of parents. We found subtle shifts in the mutation spectrum but no differences in total DNM rates among genetic ancestry groups, or between smokers and non-smokers. Testing for associations between parental mutation phenotypes and their burden of loss-of-function and deleterious missense variants in a set of 180 DNA repair and maintenance genes, we discovered that disruptions in REV1 and LIG1 increase germline mutation rates, and thus that rare mutator alleles segregate in population cohorts. ### Competing Interest Statement The authors have declared no competing interest. NIH, R35 GM083098
biorxiv.org
For an update on our preprint about the mysterious signature SBS5, see: www.biorxiv.org/content/10.1.... New analyses throughout, but see Figure 5 in particular.
biorxiv.org
Molly Przeworski@mollyprz.bsky.social · last yr.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/...
Job AD. Research Directions: 1. Selection in early development; Pop gen methods applied to new technologies, i.e. scDNA-seq with D. Shao 2. Study of hypermutability and selection using population cohorts with E. Koch 3. Evolution of Mutagenesis with M. Penenell & @jgschraiber.bsky.social
POSTDOCTORAL RESEARCHER - McDermott Center HG&D - Seplyarskiy Lab
Discover POSTDOCTORAL RESEARCHER - McDermott Center HG&D - Seplyarskiy Lab and other PostDoc jobs in Dallas, TX and apply online today!
jobs.utsouthwestern.edu
Our paper is out! Learning evolutionary parameters from genealogies using allelic trees url: academic.oup.com/genetics/art... With Aleksandra Walczak and @thierrymora.bsky.social Congrats to first author Antoine Aragon, well done Antoine!
Learning evolutionary parameters from genealogies using allelic trees
To better understand how genetic differences arise in populations of cells, Aragon et al. created a new method, which estimates how fast cells divide, die,
academic.oup.com
Happy to highlight an essay I wrote together with @marcdemanuel.bsky.social, @natanaels.bsky.social and Anastasia Stolyarova, trying to think through what sets the mutation rate of a cell type in an animal species: www.biorxiv.org/content/10.6... 1/n
What sets the mutation rate of a cell type in an animal species?
Germline mutation rates per generation are strikingly similar across animals, despite vast differences in life histories. Analogously, in at least one somatic cell type, mutation rates at the end of l...
biorxiv.org
The registration deadline is fast approaching for probgen 2026! Abstracts due by January 15, registration by January 31 probgen2026.github.io
Home - ProbGen 2026
Your Site Description
probgen2026.github.io
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...
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...
medrxiv.org
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...
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...
biorxiv.org
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.
The exciting next instalment of Mutations in Time and Space... Open for registration now
A helpful visual in many ways
Jonathan Edwards@jonathanreports.bsky.social · 12mo agoScoop: 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
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
Mutations in Time and Space — 20260413
Mutations in Time and Space
coursesandconferences.wellcomeconnectingscience.org
Mutation bias in driver genes reveals the distribution of effects of oncogenic mutations https://www.biorxiv.org/content/10.1101/2025.09.25.678277v1
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.
nature.com
Very happy to share our work on signature SBS5. See Molly's thread for a short summary
Molly Przeworski@mollyprz.bsky.social · last yr.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/...
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
PhD Student in Mutational Processes Driving Somatic Evolution
jobs.dkfz.de
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!
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
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.
Nature Reviews Genetics@natrevgenet.nature.com · last yr.New online! Making sense of the polygenicity of complex traits
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...
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 ...
biorxiv.org
Elegant new theory on polygenic adaptation by Will Milligan, Laura Heyward, and Guy Sella.
bioRxiv Evolutionary Biology@biorxiv-evobio.bsky.social · last yr.When should adaptation arise from a polygenic response versus few large effect changes? https://www.biorxiv.org/content/10.1101/2025.05.15.654234v1
Having a hard time processing this. HHMI is pausing all competitions. Very demoralizing for early career scientists like me @hhmi.org
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 ⬇️
📣 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
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?
