Natanael Spisak

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!

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

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,

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!

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...

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

The registration deadline is fast approaching for probgen 2026! Abstracts due by January 15, registration by January 31

probgen2026.github.io

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...

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...

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...

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...

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

ASHG?

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

Mutation bias in driver genes reveals the distribution of effects of oncogenic mutations https://www.biorxiv.org/content/10.1101/2025.09.25.678277v1

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.

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...

Thanks! Indeed, it seems that the NMF model assumptions are correct and there is little interaction between signatures (at least at the level of 96 mutation types). There are exceptions, such as SBS2 and SBS13, which are both due to APOBEC deamination, SBS7* signatures (UV), and then SBS5.

Very happy to share our work on signature SBS5. See Molly's thread for a short summary

PhD Student in Mutational Processes Driving Somatic Evolution

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

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!

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...

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/...

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.

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 ...

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...

Elegant new theory on polygenic adaptation by Will Milligan, Laura Heyward, and Guy Sella.

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 ⬇️

Banner for job offers

📣 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

A crowd of people wraps around a hallway. About 25-30 people are visible

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?

Do people know about the STEM Jobs feed? Seems useful to put related job postings together in one place. #ScienceJobs

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.

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...

@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/...

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...