Jonathan Frazer
@jonnyfrazer.bsky.social
Probabilistic machine learning to address questions in evolution and health #EvolutionaryMedicine. PI at the Centre for Genomic Regulation, co-leading a group with Mafalda Dias. Previously Harvard.
Pinned
Jonathan Frazer
@jonnyfrazer.bsky.social
· Nov 24
Proteome-wide model for human disease genetics
Nature Genetics - popEVE is a proteome-wide deep generative model to identify and predict pathogenicity of missense mutations causing genetic disorders.
rdcu.be
popEVE is out in Nature Genetics! 🎉
We built a proteome-wide model that combines cross-species and human population variation to rank missense variants by disease severity and help diagnose rare genetic disorders.
rdcu.be/eRu7K
We built a proteome-wide model that combines cross-species and human population variation to rank missense variants by disease severity and help diagnose rare genetic disorders.
rdcu.be/eRu7K
Bluesky doesn’t really shine yet as a place to discover papers, especially at the intersection of biology and ML. To help a little, I’m going to start sharing papers I find interesting. To kick things off, here’s one from @petar-v.bsky.social and colleagues at DeepMind
arxiv.org/abs/2601.22950
arxiv.org/abs/2601.22950
Perplexity Cannot Always Tell Right from Wrong
Perplexity -- a function measuring a model's overall level of "surprise" when encountering a particular output -- has gained significant traction in recent years, both as a loss function and as a simp...
arxiv.org
February 3, 2026 at 8:47 AM
Bluesky doesn’t really shine yet as a place to discover papers, especially at the intersection of biology and ML. To help a little, I’m going to start sharing papers I find interesting. To kick things off, here’s one from @petar-v.bsky.social and colleagues at DeepMind
arxiv.org/abs/2601.22950
arxiv.org/abs/2601.22950
Reposted by Jonathan Frazer
"Probing the Dark Energy in the Functional Protein Universe" is now published in @pnas.org 🎉
www.pnas.org/doi/10.1073/...
www.pnas.org/doi/10.1073/...
January 22, 2026 at 7:09 PM
"Probing the Dark Energy in the Functional Protein Universe" is now published in @pnas.org 🎉
www.pnas.org/doi/10.1073/...
www.pnas.org/doi/10.1073/...
Reposted by Jonathan Frazer
For no reason, I remembered today that I too once got to take a picture holding Nobel Prize that I didn't earn
January 16, 2026 at 3:14 PM
For no reason, I remembered today that I too once got to take a picture holding Nobel Prize that I didn't earn
Reposted by Jonathan Frazer
TF-MINDI is out! A new method to learn cis-regulatory codes through rich embeddings of TF binding sites. TF-MINDI decomposes motif neighbourhoods, and works downstream of any sequence-to-function deep learning model. We deeply study the enhancer code in human neural development, check out the thread
January 15, 2026 at 12:32 PM
TF-MINDI is out! A new method to learn cis-regulatory codes through rich embeddings of TF binding sites. TF-MINDI decomposes motif neighbourhoods, and works downstream of any sequence-to-function deep learning model. We deeply study the enhancer code in human neural development, check out the thread
Reposted by Jonathan Frazer
We’ve updated the EVEREST benchmark to include real-world viral evolution! www.biorxiv.org/content/10.1...
Co-led by Noor Youssef and me, along with co-authors Navami Jain, Aarushi Mehrotra, Sarrah Leung, Abigail Jackson, @deboramarks.bsky.social, and with @cepi.net @futurehousesf.bsky.social!
Co-led by Noor Youssef and me, along with co-authors Navami Jain, Aarushi Mehrotra, Sarrah Leung, Abigail Jackson, @deboramarks.bsky.social, and with @cepi.net @futurehousesf.bsky.social!
🚨New paper 🚨
Can protein language models help us fight viral outbreaks? Not yet. Here’s why 🧵👇
1/12
Can protein language models help us fight viral outbreaks? Not yet. Here’s why 🧵👇
1/12
January 13, 2026 at 7:06 PM
We’ve updated the EVEREST benchmark to include real-world viral evolution! www.biorxiv.org/content/10.1...
Co-led by Noor Youssef and me, along with co-authors Navami Jain, Aarushi Mehrotra, Sarrah Leung, Abigail Jackson, @deboramarks.bsky.social, and with @cepi.net @futurehousesf.bsky.social!
Co-led by Noor Youssef and me, along with co-authors Navami Jain, Aarushi Mehrotra, Sarrah Leung, Abigail Jackson, @deboramarks.bsky.social, and with @cepi.net @futurehousesf.bsky.social!
Reposted by Jonathan Frazer
🚨🚨🚨
We're looking for a research tech to work on alt splicing, pancreatic islets and diabetes. The goal is to set a high-throughput platform to investigate the role of alternative exons in beta cell biology!
Interested in joining our lab at @melisupf.bsky.social? 👇
www.upf.edu/documents/d/...
We're looking for a research tech to work on alt splicing, pancreatic islets and diabetes. The goal is to set a high-throughput platform to investigate the role of alternative exons in beta cell biology!
Interested in joining our lab at @melisupf.bsky.social? 👇
www.upf.edu/documents/d/...
www.upf.edu
December 23, 2025 at 12:36 PM
🚨🚨🚨
We're looking for a research tech to work on alt splicing, pancreatic islets and diabetes. The goal is to set a high-throughput platform to investigate the role of alternative exons in beta cell biology!
Interested in joining our lab at @melisupf.bsky.social? 👇
www.upf.edu/documents/d/...
We're looking for a research tech to work on alt splicing, pancreatic islets and diabetes. The goal is to set a high-throughput platform to investigate the role of alternative exons in beta cell biology!
Interested in joining our lab at @melisupf.bsky.social? 👇
www.upf.edu/documents/d/...
Reposted by Jonathan Frazer
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...
LFB is NeurIPS-bound! 🎉
Mafalda, @cwjpugh.bsky.social and I will be in San Diego next week for NeurIPS -- happy to chat variant effect prediction (or just say hi).
“From Likelihood to Fitness: Improving Variant Effect Prediction in Protein and Genome Language Models”
openreview.net/pdf/a151f62e...
Mafalda, @cwjpugh.bsky.social and I will be in San Diego next week for NeurIPS -- happy to chat variant effect prediction (or just say hi).
“From Likelihood to Fitness: Improving Variant Effect Prediction in Protein and Genome Language Models”
openreview.net/pdf/a151f62e...
openreview.net
November 25, 2025 at 11:55 AM
LFB is NeurIPS-bound! 🎉
Mafalda, @cwjpugh.bsky.social and I will be in San Diego next week for NeurIPS -- happy to chat variant effect prediction (or just say hi).
“From Likelihood to Fitness: Improving Variant Effect Prediction in Protein and Genome Language Models”
openreview.net/pdf/a151f62e...
Mafalda, @cwjpugh.bsky.social and I will be in San Diego next week for NeurIPS -- happy to chat variant effect prediction (or just say hi).
“From Likelihood to Fitness: Improving Variant Effect Prediction in Protein and Genome Language Models”
openreview.net/pdf/a151f62e...
Reposted by Jonathan Frazer
New paper “Proteome-wide model for human disease genetics” is now live at Nature Genetics: rdcu.be/eRu7K
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
November 24, 2025 at 2:53 PM
New paper “Proteome-wide model for human disease genetics” is now live at Nature Genetics: rdcu.be/eRu7K
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
popEVE is out in Nature Genetics! 🎉
We built a proteome-wide model that combines cross-species and human population variation to rank missense variants by disease severity and help diagnose rare genetic disorders.
rdcu.be/eRu7K
We built a proteome-wide model that combines cross-species and human population variation to rank missense variants by disease severity and help diagnose rare genetic disorders.
rdcu.be/eRu7K
Proteome-wide model for human disease genetics
Nature Genetics - popEVE is a proteome-wide deep generative model to identify and predict pathogenicity of missense mutations causing genetic disorders.
rdcu.be
November 24, 2025 at 1:35 PM
popEVE is out in Nature Genetics! 🎉
We built a proteome-wide model that combines cross-species and human population variation to rank missense variants by disease severity and help diagnose rare genetic disorders.
rdcu.be/eRu7K
We built a proteome-wide model that combines cross-species and human population variation to rank missense variants by disease severity and help diagnose rare genetic disorders.
rdcu.be/eRu7K
PopEVE covered by @financialtimes.com today! www.ft.com/content/bc49...
New AI model enhances diagnosis of rare diseases
PopEVE system outperformed rivals such as Google DeepMind’s AlphaMissense
www.ft.com
November 24, 2025 at 10:23 AM
PopEVE covered by @financialtimes.com today! www.ft.com/content/bc49...
Reposted by Jonathan Frazer
Today we introduce Mafalda Dias and @jonnyfrazer.bsky.social from CentreGenomic Regulation @crg.eu ,with one PhD position open in their lab.
Learn more about the PhD programme and how to apply → www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #Genomics #EvolutionaryBiology
Learn more about the PhD programme and how to apply → www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #Genomics #EvolutionaryBiology
November 18, 2025 at 9:12 AM
Today we introduce Mafalda Dias and @jonnyfrazer.bsky.social from CentreGenomic Regulation @crg.eu ,with one PhD position open in their lab.
Learn more about the PhD programme and how to apply → www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #Genomics #EvolutionaryBiology
Learn more about the PhD programme and how to apply → www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #Genomics #EvolutionaryBiology
🚨 Two weeks left to apply!
Applications are open for the @crg_eu PhD Programme! 20 fully funded positions — including one in our group through the Evolutionary Medical Genomics ITN.
Join us to develop deep generative models of cross-species data to tackle open questions in disease genetics.
www.crg.eu/en/content/t...
Join us to develop deep generative models of cross-species data to tackle open questions in disease genetics.
www.crg.eu/en/content/t...
November 17, 2025 at 8:28 AM
🚨 Two weeks left to apply!
Reposted by Jonathan Frazer
🚨 15 days left to apply!
Be part of EvoMG-DN and advance your PhD career in evolutionary genomics.
👉 www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #BiomedicalResearch #Genomics #EvolutionaryBiology #MSCA #HorizonEurope #EUResearch #ResearchOpportunities #PhDPositions
Be part of EvoMG-DN and advance your PhD career in evolutionary genomics.
👉 www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #BiomedicalResearch #Genomics #EvolutionaryBiology #MSCA #HorizonEurope #EUResearch #ResearchOpportunities #PhDPositions
November 14, 2025 at 10:19 AM
🚨 15 days left to apply!
Be part of EvoMG-DN and advance your PhD career in evolutionary genomics.
👉 www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #BiomedicalResearch #Genomics #EvolutionaryBiology #MSCA #HorizonEurope #EUResearch #ResearchOpportunities #PhDPositions
Be part of EvoMG-DN and advance your PhD career in evolutionary genomics.
👉 www.evomg-dn.eu
#PhD #DoctoralTraining #ResearchCareers #LifeSciences #BiomedicalResearch #Genomics #EvolutionaryBiology #MSCA #HorizonEurope #EUResearch #ResearchOpportunities #PhDPositions
Reposted by Jonathan Frazer
🚀 Excited to share our preprint scConcept: a contrastive pretraining framework for technology-agnostic single-cell representations.
We move beyond reconstruction to learn rich, cell-level embeddings for diverse omics.
📘 www.biorxiv.org/content/10.1...
We move beyond reconstruction to learn rich, cell-level embeddings for diverse omics.
📘 www.biorxiv.org/content/10.1...
scConcept: Contrastive pretraining for technology-agnostic single-cell representations beyond reconstruction
Recent large-scale single-cell foundation models have shown promise for exploring cellular states, yet they often underperform compared to simpler, domain-specific methods, raising concerns about…
www.biorxiv.org
November 13, 2025 at 5:17 PM
🚀 Excited to share our preprint scConcept: a contrastive pretraining framework for technology-agnostic single-cell representations.
We move beyond reconstruction to learn rich, cell-level embeddings for diverse omics.
📘 www.biorxiv.org/content/10.1...
We move beyond reconstruction to learn rich, cell-level embeddings for diverse omics.
📘 www.biorxiv.org/content/10.1...
Reposted by Jonathan Frazer
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 Jonathan Frazer
(1/N) Thrilled to share that our paper HiPoNet (High dimensional Point cloud Network) to be presented at NeurIPS 2025! HiPoNet treats an entire high-dimensional point cloud as a datapoint! It captures multi-scale geometry and topology of the cloud perform classification and regression tasks.
November 7, 2025 at 2:09 PM
(1/N) Thrilled to share that our paper HiPoNet (High dimensional Point cloud Network) to be presented at NeurIPS 2025! HiPoNet treats an entire high-dimensional point cloud as a datapoint! It captures multi-scale geometry and topology of the cloud perform classification and regression tasks.
Reposted by Jonathan Frazer
More than two decades have passed since we discovered that rare disruptions of the FOXP2 gene disturb development of proficient speech/language skills. Today we know of multiple FOXP genes that are directly implicated in distinct brain-related conditions with differences in symptoms & severity.🧪 1/n
October 29, 2025 at 5:09 PM
More than two decades have passed since we discovered that rare disruptions of the FOXP2 gene disturb development of proficient speech/language skills. Today we know of multiple FOXP genes that are directly implicated in distinct brain-related conditions with differences in symptoms & severity.🧪 1/n
Reposted by Jonathan Frazer
Our review is out in Nature Reviews Genetics! rdcu.be/d5AY2
We show how phylogeny-based methods can resolve the problem of non-independence in genomic datasets.
These methods must be considered an essential part of the comparative genomics toolkit.
@lauriebelch.bsky.social @stuwest.bsky.social
We show how phylogeny-based methods can resolve the problem of non-independence in genomic datasets.
These methods must be considered an essential part of the comparative genomics toolkit.
@lauriebelch.bsky.social @stuwest.bsky.social
A phylogenetic approach to comparative genomics
Nature Reviews Genetics - Controlling for phylogeny is essential in comparative genomics studies, because species, genomes and genes are not independent data points within statistical tests. The...
rdcu.be
January 8, 2025 at 1:19 PM
Our review is out in Nature Reviews Genetics! rdcu.be/d5AY2
We show how phylogeny-based methods can resolve the problem of non-independence in genomic datasets.
These methods must be considered an essential part of the comparative genomics toolkit.
@lauriebelch.bsky.social @stuwest.bsky.social
We show how phylogeny-based methods can resolve the problem of non-independence in genomic datasets.
These methods must be considered an essential part of the comparative genomics toolkit.
@lauriebelch.bsky.social @stuwest.bsky.social
Reposted by Jonathan Frazer
Now online @nature.com!
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Designing allosteric modulators to change GPCR G protein subtype selectivity - Nature
Studies of the G-protein-coupled receptor NTSR1 show that the G protein selectivity of this receptor can be modified by small molecules, enabling the design of drugs that work by switching receptor su...
www.nature.com
October 27, 2025 at 8:50 PM
Now online @nature.com!
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Want to change the consequences of receptor activation?
Small molecules binding the GPCR-transducer interface change G protein subtype preference in predictable ways, enabling rational drug design 💥
So many new possibilities! 🧪🧠🟦
www.nature.com/articles/s41...
🧵👇
Applications are open for the @crg_eu PhD Programme! 20 fully funded positions — including one in our group through the Evolutionary Medical Genomics ITN.
Join us to develop deep generative models of cross-species data to tackle open questions in disease genetics.
www.crg.eu/en/content/t...
Join us to develop deep generative models of cross-species data to tackle open questions in disease genetics.
www.crg.eu/en/content/t...
October 23, 2025 at 11:01 AM
Applications are open for the @crg_eu PhD Programme! 20 fully funded positions — including one in our group through the Evolutionary Medical Genomics ITN.
Join us to develop deep generative models of cross-species data to tackle open questions in disease genetics.
www.crg.eu/en/content/t...
Join us to develop deep generative models of cross-species data to tackle open questions in disease genetics.
www.crg.eu/en/content/t...
Reposted by Jonathan Frazer
Announcing our new protein design server evedesign.bio:
• End-to-end protein design for everyone!
• Analyze your generated library interactively and on 3D structures
• Export codon-optimized DNA sequences for experimental testing.
• End-to-end protein design for everyone!
• Analyze your generated library interactively and on 3D structures
• Export codon-optimized DNA sequences for experimental testing.
October 22, 2025 at 2:17 PM
Announcing our new protein design server evedesign.bio:
• End-to-end protein design for everyone!
• Analyze your generated library interactively and on 3D structures
• Export codon-optimized DNA sequences for experimental testing.
• End-to-end protein design for everyone!
• Analyze your generated library interactively and on 3D structures
• Export codon-optimized DNA sequences for experimental testing.
Reposted by Jonathan Frazer
The second session (Thr 09/10, morning) was dedicated to the Genomic Basis & History of Disease.
October 12, 2025 at 1:48 PM
The second session (Thr 09/10, morning) was dedicated to the Genomic Basis & History of Disease.
Reposted by Jonathan Frazer
I adored writing this piece. It brings together several of the things preoccupying me right now, like chromatin organization and gene regulation. There's so much more to be said on that. Also, these marine critters look gorgeous.
www.quantamagazine.org/loops-of-dna...
www.quantamagazine.org/loops-of-dna...
Loops of DNA Equipped Ancient Life To Become Complex | Quanta Magazine
New work shows that physical folding of the genome to control genes located far away may have been an early evolutionary development.
www.quantamagazine.org
October 8, 2025 at 2:21 PM
I adored writing this piece. It brings together several of the things preoccupying me right now, like chromatin organization and gene regulation. There's so much more to be said on that. Also, these marine critters look gorgeous.
www.quantamagazine.org/loops-of-dna...
www.quantamagazine.org/loops-of-dna...
The most beautiful data is on the horizon!
Happy to share the Biodiversity Cell Atlas white paper, out today in @nature.com. We look at the possibilities, challenges, and potential impacts of molecularly mapping cells across the tree of life.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
September 24, 2025 at 4:26 PM
The most beautiful data is on the horizon!