Jeff Spence
@jeffspence.github.io
assistant professor at ucsf interested in genetics, statistics, etc…
jeffspence.github.io
jeffspence.github.io
Pinned
Specificity, length and luck drive gene rankings in association studies - Nature
Genetic association tests prioritize candidate genes based on different criteria.
www.nature.com
How do GWAS and rare variant burden tests rank gene signals?
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
Reposted by Jeff Spence
Transcription start sites show a strong influx of heritable variants arising in early development.
Our new paper is now in Nat. Comms: www.nature.com/articles/s41...
It would be interesting to see this effect in the new mosaic-mutation dataset from @r-rahbari.bsky.social and @isaacgs94.bsky.social.
Our new paper is now in Nat. Comms: www.nature.com/articles/s41...
It would be interesting to see this effect in the new mosaic-mutation dataset from @r-rahbari.bsky.social and @isaacgs94.bsky.social.
November 26, 2025 at 10:45 PM
Transcription start sites show a strong influx of heritable variants arising in early development.
Our new paper is now in Nat. Comms: www.nature.com/articles/s41...
It would be interesting to see this effect in the new mosaic-mutation dataset from @r-rahbari.bsky.social and @isaacgs94.bsky.social.
Our new paper is now in Nat. Comms: www.nature.com/articles/s41...
It would be interesting to see this effect in the new mosaic-mutation dataset from @r-rahbari.bsky.social and @isaacgs94.bsky.social.
Reposted by Jeff Spence
Work from my amazing undergrad @leyan-wang.bsky.social is just preprinted! TL;DR: If you worry that ARG methods might fail on unphased data due to phasing errors, you may not need to.
Check it out & consider reposting to support a great young scientist!
Check it out & consider reposting to support a great young scientist!
We are excited to share our recent work on the surprising robustness of Ancestral Recombination Graph (ARG) inference tools to computational phasing errors, now available on BioRxiv: biorxiv.org/content/10.1....
This work is co-advised by @yundeng.bsky.social and Rasmus Nielsen.
1/7
This work is co-advised by @yundeng.bsky.social and Rasmus Nielsen.
1/7
Robustness of Ancestral Recombination Graph Inference Tools to Phasing Errors
Ancestral Recombination Graphs (ARGs) are fundamental population genetic structures that encode the genealogical history of a sample of haplotypes along the genome. They have recently received substan...
biorxiv.org
November 26, 2025 at 5:12 PM
Work from my amazing undergrad @leyan-wang.bsky.social is just preprinted! TL;DR: If you worry that ARG methods might fail on unphased data due to phasing errors, you may not need to.
Check it out & consider reposting to support a great young scientist!
Check it out & consider reposting to support a great young scientist!
Reposted by Jeff Spence
We are excited to share our recent work on the surprising robustness of Ancestral Recombination Graph (ARG) inference tools to computational phasing errors, now available on BioRxiv: biorxiv.org/content/10.1....
This work is co-advised by @yundeng.bsky.social and Rasmus Nielsen.
1/7
This work is co-advised by @yundeng.bsky.social and Rasmus Nielsen.
1/7
Robustness of Ancestral Recombination Graph Inference Tools to Phasing Errors
Ancestral Recombination Graphs (ARGs) are fundamental population genetic structures that encode the genealogical history of a sample of haplotypes along the genome. They have recently received substan...
biorxiv.org
November 26, 2025 at 5:09 PM
We are excited to share our recent work on the surprising robustness of Ancestral Recombination Graph (ARG) inference tools to computational phasing errors, now available on BioRxiv: biorxiv.org/content/10.1....
This work is co-advised by @yundeng.bsky.social and Rasmus Nielsen.
1/7
This work is co-advised by @yundeng.bsky.social and Rasmus Nielsen.
1/7
Reposted by Jeff Spence
The last work of my PhD is finally out: www.pnas.org/doi/10.1073/...! This work is about accurately estimating branch length in the Ancestral Recombination Graph (ARG), which is achieved by a really simple framework with minimal assumptions. (1/n)
PNAS
Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...
www.pnas.org
November 25, 2025 at 8:27 PM
The last work of my PhD is finally out: www.pnas.org/doi/10.1073/...! This work is about accurately estimating branch length in the Ancestral Recombination Graph (ARG), which is achieved by a really simple framework with minimal assumptions. (1/n)
Reposted by Jeff Spence
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 Jeff Spence
📣📣📣 Excited for our lab's latest preprint, led by Chief Ben-Eghan! www.medrxiv.org/content/10.1...
tl;dr We identify protein vQTLs in multiple ancestries then use MVMR to show independent effects of mean & variance on disease, suggesting targeting protein variance could have therapeutic potential.
tl;dr We identify protein vQTLs in multiple ancestries then use MVMR to show independent effects of mean & variance on disease, suggesting targeting protein variance could have therapeutic potential.
November 22, 2025 at 11:42 AM
📣📣📣 Excited for our lab's latest preprint, led by Chief Ben-Eghan! www.medrxiv.org/content/10.1...
tl;dr We identify protein vQTLs in multiple ancestries then use MVMR to show independent effects of mean & variance on disease, suggesting targeting protein variance could have therapeutic potential.
tl;dr We identify protein vQTLs in multiple ancestries then use MVMR to show independent effects of mean & variance on disease, suggesting targeting protein variance could have therapeutic potential.
Reposted by Jeff Spence
The Genomic History Inference Strategies Tournament closes in 1 week! Learn, test yourself, and help the community by trying to infer demographic history detect sweeps! ghist.bio
November 21, 2025 at 4:20 PM
The Genomic History Inference Strategies Tournament closes in 1 week! Learn, test yourself, and help the community by trying to infer demographic history detect sweeps! ghist.bio
Reposted by Jeff Spence
In an earlier project simulating quantitative traits/stabilizing selection in a human-Neanderthal model, I became a bit curious about some observed fitness dynamics that I wasn’t expecting.
I’m not sure if this is all that interesting or relevant, but at least it’s short.
I’m not sure if this is all that interesting or relevant, but at least it’s short.
Mean fitness is maximized in small populations under stabilizing selection on highly polygenic traits https://www.biorxiv.org/content/10.1101/2025.11.17.688329v1
November 21, 2025 at 11:09 AM
In an earlier project simulating quantitative traits/stabilizing selection in a human-Neanderthal model, I became a bit curious about some observed fitness dynamics that I wasn’t expecting.
I’m not sure if this is all that interesting or relevant, but at least it’s short.
I’m not sure if this is all that interesting or relevant, but at least it’s short.
Reposted by Jeff Spence
Wisconsin Evolution is accepting applications for our Seminar Series' Early Career Scientist Award. Come share your evolution research and visit UW-Madison's evolution community. Open to grad students and postdocs (<5 yrs post PhD) from outside UW-Madison.
Apply by Dec 15th here: shorturl.at/4a4O6
Apply by Dec 15th here: shorturl.at/4a4O6
Early Career Scientist Awards 2026
Application to the UW-Madison Evolution Seminar Series - Early Career Scientist Awards.
urldefense.com
November 19, 2025 at 8:55 PM
Wisconsin Evolution is accepting applications for our Seminar Series' Early Career Scientist Award. Come share your evolution research and visit UW-Madison's evolution community. Open to grad students and postdocs (<5 yrs post PhD) from outside UW-Madison.
Apply by Dec 15th here: shorturl.at/4a4O6
Apply by Dec 15th here: shorturl.at/4a4O6
@hakha.bsky.social and I wrote a Research Briefing (with a lay summary + "behind the scenes") of our paper on how genes are prioritized by GWAS and rare variant burden tests. 🧬🧪
www.nature.com/articles/d41...
www.nature.com/articles/d41...
How do genetic association studies rank genes?
Genome-wide association studies and rare-variant burden tests reveal complementary aspects of trait biology.
www.nature.com
November 19, 2025 at 6:43 PM
@hakha.bsky.social and I wrote a Research Briefing (with a lay summary + "behind the scenes") of our paper on how genes are prioritized by GWAS and rare variant burden tests. 🧬🧪
www.nature.com/articles/d41...
www.nature.com/articles/d41...
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 Jeff Spence
My center at NYU SoM is hiring an Assistant/Associate Professor in human genetics and genomics. It's a wonderful place to do science. Please apply or pass along. apply.interfolio.com/177375
Apply - Interfolio
{{$ctrl.$state.data.pageTitle}} - Apply - Interfolio
apply.interfolio.com
November 14, 2025 at 3:51 PM
My center at NYU SoM is hiring an Assistant/Associate Professor in human genetics and genomics. It's a wonderful place to do science. Please apply or pass along. apply.interfolio.com/177375
Reposted by Jeff Spence
Yes! And also we have an exciting announcement - we are so lucky to have the privilege of having Brenna Henn give the keynote. hennlab.ucdavis.edu
November 13, 2025 at 8:37 PM
Yes! And also we have an exciting announcement - we are so lucky to have the privilege of having Brenna Henn give the keynote. hennlab.ucdavis.edu
Reposted by Jeff Spence
I am so excited to share new work on a TE insertion that regulates iridescence in swordtails, led by fantastic grad student @nadiahaghani.bsky.social and with help from many coauthors! In a time that has been so difficult to navigate, this & other projects have kept my spirits up: shorturl.at/NE65A
Insertion of an invading retrovirus regulates a novel color trait in swordtail fish
For over a century, evolutionary biologists have been motivated to understand the mechanisms through which organisms adapt to their environments. Coloration and pigmentation are remarkably variable wi...
shorturl.at
November 12, 2025 at 8:34 PM
I am so excited to share new work on a TE insertion that regulates iridescence in swordtails, led by fantastic grad student @nadiahaghani.bsky.social and with help from many coauthors! In a time that has been so difficult to navigate, this & other projects have kept my spirits up: shorturl.at/NE65A
Reposted by Jeff Spence
First time on Bsky and first big announcement!
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
Estimation and mapping of the missing heritability of human phenotypes - Nature
WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 co...
www.nature.com
November 12, 2025 at 5:57 PM
First time on Bsky and first big announcement!
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.
Our manuscript is here: www.nature.com/articles/s41....
Reposted by Jeff Spence
An empirical approach to evaluating the prevalence of long-lived balancing selection in humans--and important limitations. Work by @hannahmm.bsky.social
November 11, 2025 at 7:14 PM
An empirical approach to evaluating the prevalence of long-lived balancing selection in humans--and important limitations. Work by @hannahmm.bsky.social
Reposted by Jeff Spence
Super excited that the bulk of my PhD work is now preprinted! Here we used whole-community competition, or coalescence, experiments to quantify selection acting on genetically diverged strains within larger communities. (1/n)
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
www.biorxiv.org
November 11, 2025 at 5:15 PM
Super excited that the bulk of my PhD work is now preprinted! Here we used whole-community competition, or coalescence, experiments to quantify selection acting on genetically diverged strains within larger communities. (1/n)
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Jeff Spence
New preprint by Hannah Munby and @mollyprz.bsky.social:
“Revisiting the evidence for long-lived balancing selection in humans” 🧪🧬
www.biorxiv.org/content/10.1...
“Revisiting the evidence for long-lived balancing selection in humans” 🧪🧬
www.biorxiv.org/content/10.1...
Revisiting the evidence for long-lived balancing selection in humans.
Balancing selection maintains variation in a population longer than expected under neutrality. In humans, there are dozens of tentative candidate loci for balancing selection, but only a handful of we...
www.biorxiv.org
November 11, 2025 at 1:06 PM
New preprint by Hannah Munby and @mollyprz.bsky.social:
“Revisiting the evidence for long-lived balancing selection in humans” 🧪🧬
www.biorxiv.org/content/10.1...
“Revisiting the evidence for long-lived balancing selection in humans” 🧪🧬
www.biorxiv.org/content/10.1...
Reposted by Jeff Spence
Introducing Nona! 🧬 @suragnair.bsky.social 's brilliant idea to unify siloed genomic AI. Nona learns jointly from DNA seq + functional data, enabling new ways of modeling genomic data!
November 10, 2025 at 9:03 PM
Introducing Nona! 🧬 @suragnair.bsky.social 's brilliant idea to unify siloed genomic AI. Nona learns jointly from DNA seq + functional data, enabling new ways of modeling genomic data!
Reposted by Jeff Spence
Nature research paper: Specificity, length and luck drive gene rankings in association studies
go.nature.com/47Fsqax
go.nature.com/47Fsqax
Specificity, length and luck drive gene rankings in association studies - Nature
Genetic association tests prioritize candidate genes based on different criteria.
go.nature.com
November 10, 2025 at 11:36 AM
Nature research paper: Specificity, length and luck drive gene rankings in association studies
go.nature.com/47Fsqax
go.nature.com/47Fsqax
Reposted by Jeff Spence
I'm on the academic job market!
I design and analyze probabilistic machine-learning methods---motivated by real-world scientific constraints, and developed in collaboration with scientists in biology, chemistry, and physics.
A few highlights of my research areas are:
I design and analyze probabilistic machine-learning methods---motivated by real-world scientific constraints, and developed in collaboration with scientists in biology, chemistry, and physics.
A few highlights of my research areas are:
November 7, 2025 at 2:47 PM
I'm on the academic job market!
I design and analyze probabilistic machine-learning methods---motivated by real-world scientific constraints, and developed in collaboration with scientists in biology, chemistry, and physics.
A few highlights of my research areas are:
I design and analyze probabilistic machine-learning methods---motivated by real-world scientific constraints, and developed in collaboration with scientists in biology, chemistry, and physics.
A few highlights of my research areas are:
Reposted by Jeff Spence
¿Hiciste tu doctorado en México? ¿Quieres hacer un postdoc en California? ¿Te interesa la genética evolutiva? ¡Checa esta beca y mándame un mensaje! alianzamx.universityofcalifornia.edu/research-and...
Postdoctoral Research Fellowships - University of California Alianza MX
Submitting an Application Current Fellows 2025 Cohort Additional Information Humberger Toggle Menu Interested in applying for a Postdoctoral Research Fellowship? Eligibility The program seeks applican...
alianzamx.universityofcalifornia.edu
November 7, 2025 at 10:47 PM
¿Hiciste tu doctorado en México? ¿Quieres hacer un postdoc en California? ¿Te interesa la genética evolutiva? ¡Checa esta beca y mándame un mensaje! alianzamx.universityofcalifornia.edu/research-and...
Reposted by Jeff Spence
Our new manuscript, led by Emily Corrigan, examines inhibitory neuron diversity across approximately 160 million years of evolutionary divergence, as part of BRAIN Initiative Cell Atlas Network (BICAN) developing brain atlas package: www.nature.com/articles/s41...
Conservation and alteration of mammalian striatal interneurons - Nature
An analysis of cell-type diversity in brain samples from a variety of mammalian species, both during development and in adult animals, reveals that the TAC3 initial class of striatal interneurons is c...
www.nature.com
November 7, 2025 at 6:06 PM
Our new manuscript, led by Emily Corrigan, examines inhibitory neuron diversity across approximately 160 million years of evolutionary divergence, as part of BRAIN Initiative Cell Atlas Network (BICAN) developing brain atlas package: www.nature.com/articles/s41...
Reposted by Jeff Spence
Exciting new study led by @ekerdoncuff.bsky.social and @meaghanmarohn.bsky.social on the evolution of Lactase Persistence in South Asia.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Revisiting the Evolution of Lactase Persistence: Insights from South Asian Genomes
Lactase persistence (LP), the ability to digest lactose from milk into adulthood, is a classic example of natural selection in humans. Multiple mutations upstream of the LCT gene are associated with L...
www.biorxiv.org
November 7, 2025 at 2:33 PM
Exciting new study led by @ekerdoncuff.bsky.social and @meaghanmarohn.bsky.social on the evolution of Lactase Persistence in South Asia.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Jeff Spence
Super interesting thread and paper
How do GWAS and rare variant burden tests rank gene signals?
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck!
🧬🧪🧵
www.nature.com/articles/s41...
Specificity, length and luck drive gene rankings in association studies - Nature
Genetic association tests prioritize candidate genes based on different criteria.
www.nature.com
November 7, 2025 at 5:29 AM
Super interesting thread and paper