Amit Sud
@amitsud.bsky.social
haemato-oncologist & wellcometrust early career fellow. @danafarber.bsky.social. @broadinstitute.org. @harvardmed.bsky.social. @universityofoxford.bsky.social. @icrlondon.bsky.social. 🧬🔴🔬💻🚴🏽♂️🥁🌱🌍
Reposted by Amit Sud
We are excited to announce our latest publication in #BloodCancerJournal of our Two-Sample MR analysis to investigate causal relationships between 446 immune cell traits and 6 B-cell malignancies
📄 www.nature.com/articles/s41...
#cancer #genetics #Bcell #bloodcancer #drugdiscovery #MR
📄 www.nature.com/articles/s41...
#cancer #genetics #Bcell #bloodcancer #drugdiscovery #MR
Mendelian randomization of immune cell phenotypes to discover potential drug targets for B-cell malignancy - Blood Cancer Journal
Blood Cancer Journal - Mendelian randomization of immune cell phenotypes to discover potential drug targets for B-cell malignancy
www.nature.com
April 16, 2025 at 11:52 AM
We are excited to announce our latest publication in #BloodCancerJournal of our Two-Sample MR analysis to investigate causal relationships between 446 immune cell traits and 6 B-cell malignancies
📄 www.nature.com/articles/s41...
#cancer #genetics #Bcell #bloodcancer #drugdiscovery #MR
📄 www.nature.com/articles/s41...
#cancer #genetics #Bcell #bloodcancer #drugdiscovery #MR
Reposted by Amit Sud
It's not all work and no play in the Houlston Lab. We had our annual #Easter taste test! Returning to hot cross buns this year. We went a bit maverick and allowed some more ... unconventional varieties!
#hotcrossbuns #tastetests
📸: @jessicamayh.bsky.social
#hotcrossbuns #tastetests
📸: @jessicamayh.bsky.social
April 17, 2025 at 3:20 PM
It's not all work and no play in the Houlston Lab. We had our annual #Easter taste test! Returning to hot cross buns this year. We went a bit maverick and allowed some more ... unconventional varieties!
#hotcrossbuns #tastetests
📸: @jessicamayh.bsky.social
#hotcrossbuns #tastetests
📸: @jessicamayh.bsky.social
Reposted by Amit Sud
Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵
Design principles of cell-state-specific enhancers in hematopoiesis
Screen of minimalistic enhancers in blood progenitor cells demonstrates widespread
dual activator-repressor function of transcription factors (TFs) and enables the model-guided
design of cell-state-sp...
www.cell.com
May 8, 2025 at 4:07 PM
Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵
🧬🩸 screen of fully synthetic enhancers in blood progenitors
🤖 AI that creates new cell state specific enhancers
🔍 negative synergies between TFs lead to specificity!
www.cell.com/cell/fulltex...
🧵
Reposted by Amit Sud
Spatial transcriptomics holds great promise to understand biological tissue function, but the assignment of transcripts to cells has been a substantial bottleneck.
For this reason, Elyas Heidari, a student in my lab and in @steglelab.bsky.social built segger.
www.biorxiv.org/content/10.1...
For this reason, Elyas Heidari, a student in my lab and in @steglelab.bsky.social built segger.
www.biorxiv.org/content/10.1...
March 17, 2025 at 4:19 PM
Spatial transcriptomics holds great promise to understand biological tissue function, but the assignment of transcripts to cells has been a substantial bottleneck.
For this reason, Elyas Heidari, a student in my lab and in @steglelab.bsky.social built segger.
www.biorxiv.org/content/10.1...
For this reason, Elyas Heidari, a student in my lab and in @steglelab.bsky.social built segger.
www.biorxiv.org/content/10.1...
Reposted by Amit Sud
Using a photonic network interface, scientists from Oxford University have successfully linked two separate quantum processors to form a single, fully connected quantum computer, paving the way to tackling computational challenges previously out of reach.
More info ⬇️
More info ⬇️
First distributed quantum algorithm brings quantum supercomputers
In a milestone that brings quantum computing tangibly closer to large-scale practical use, scientists at Oxford University’s Department of Physics have demonstrated the first instance of distributed
www.ox.ac.uk
February 6, 2025 at 11:49 AM
Using a photonic network interface, scientists from Oxford University have successfully linked two separate quantum processors to form a single, fully connected quantum computer, paving the way to tackling computational challenges previously out of reach.
More info ⬇️
More info ⬇️
Reposted by Amit Sud
Delighted to share our latest paper describing a method to read the levels of hundreds of metabolites or drugs in parallel using DNA sequencing. This method, which we call ‘smol-seq’ (Small MOLecule sequencing), harnesses the power of DNA sequencing for metabolite detection:
rdcu.be/d8xLv (1/6)
rdcu.be/d8xLv (1/6)
Quantifying metabolites using structure-switching aptamers coupled to DNA sequencing
Nature Biotechnology - Metabolites can be quantified using a combination of aptamers and DNA barcodes.
rdcu.be
February 4, 2025 at 1:54 PM
Delighted to share our latest paper describing a method to read the levels of hundreds of metabolites or drugs in parallel using DNA sequencing. This method, which we call ‘smol-seq’ (Small MOLecule sequencing), harnesses the power of DNA sequencing for metabolite detection:
rdcu.be/d8xLv (1/6)
rdcu.be/d8xLv (1/6)
Reposted by Amit Sud
Now out in @science.org w/ @jshendure.bsky.social we present 'Genome-shuffle-seq': a method to shuffle mammalian genomes and characterize the impact of structural variants (SVs) with single-cell resolution in one experiment.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Multiplex generation and single-cell analysis of structural variants in mammalian genomes
Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) ...
www.science.org
January 31, 2025 at 7:41 PM
Now out in @science.org w/ @jshendure.bsky.social we present 'Genome-shuffle-seq': a method to shuffle mammalian genomes and characterize the impact of structural variants (SVs) with single-cell resolution in one experiment.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by Amit Sud
Beware! AAV libraries prone to length & homology dependent chimerism! Our latest preprint, from the brilliant @jblalanne.bsky.social, was a true surprise as related phenomena are textbook for lentivirus (highly relevant to HIV & Perturb-seq) yet to our reading not known for AAV tinyurl.com/5amc562a
January 17, 2025 at 6:17 PM
Beware! AAV libraries prone to length & homology dependent chimerism! Our latest preprint, from the brilliant @jblalanne.bsky.social, was a true surprise as related phenomena are textbook for lentivirus (highly relevant to HIV & Perturb-seq) yet to our reading not known for AAV tinyurl.com/5amc562a
Reposted by Amit Sud
We're delighted to share our work on scrambling the human genome using prime editing, repetitive elements, and recombinases in @science.org , led by @jonaskoeppel.bsky.social , @f-raphael.bsky.social , with @proftomellis.bsky.social and George Church.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Randomizing the human genome by engineering recombination between repeat elements
We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into re...
www.science.org
January 31, 2025 at 1:49 PM
We're delighted to share our work on scrambling the human genome using prime editing, repetitive elements, and recombinases in @science.org , led by @jonaskoeppel.bsky.social , @f-raphael.bsky.social , with @proftomellis.bsky.social and George Church.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by Amit Sud
Excited to present our work on developing jaxQTL, a fast single-cell eQTL mapping tool that improves power and robustness in identifying sc-eQTLs using count-based models. See details in threads 🧵
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
Efficient count-based models improve power and robustness for large-scale single-cell eQTL mapping
Population-scale single-cell transcriptomic technologies (scRNA-seq) enable characterizing variant effects on gene regulation at the cellular level (e.g., single-cell eQTLs; sc-eQTLs). However, existi...
www.medrxiv.org
January 27, 2025 at 6:29 PM
Excited to present our work on developing jaxQTL, a fast single-cell eQTL mapping tool that improves power and robustness in identifying sc-eQTLs using count-based models. See details in threads 🧵
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
Reposted by Amit Sud
I posted a couple days ago about our new paper on building causal graphs from genetic associations + Perturb-seq.
Here I want to expand on the value of using DIRECTIONAL information contained in LoF burden tests.🧵
[work led by @minetoota.bsky.social ]
bsky.app/profile/jkpr...
Here I want to expand on the value of using DIRECTIONAL information contained in LoF burden tests.🧵
[work led by @minetoota.bsky.social ]
bsky.app/profile/jkpr...
GWAS provides a unique tool in human biology as it can establish causal links from variants to trait.
But interpretation is difficult as most effects flow through (unobserved) gene regulatory networks. Can we gain insight by linking to modern Perturb-seq data?
www.biorxiv.org/content/10.1...
But interpretation is difficult as most effects flow through (unobserved) gene regulatory networks. Can we gain insight by linking to modern Perturb-seq data?
www.biorxiv.org/content/10.1...
Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq
Genetic association studies provide a unique tool for identifying causal links from genes to human traits and diseases. However, it is challenging to determine the biological mechanisms underlying mos...
www.biorxiv.org
January 27, 2025 at 7:19 PM
I posted a couple days ago about our new paper on building causal graphs from genetic associations + Perturb-seq.
Here I want to expand on the value of using DIRECTIONAL information contained in LoF burden tests.🧵
[work led by @minetoota.bsky.social ]
bsky.app/profile/jkpr...
Here I want to expand on the value of using DIRECTIONAL information contained in LoF burden tests.🧵
[work led by @minetoota.bsky.social ]
bsky.app/profile/jkpr...
Reposted by Amit Sud
How population stratification makes environments look like genes. A short 🧵:
January 20, 2025 at 7:09 PM
How population stratification makes environments look like genes. A short 🧵:
Reposted by Amit Sud
The death of the surrealist film and television director David Lynch inspired tributes from fellow filmmakers, celebrities and past collaborators, who praised his visionary work and singular voice.
The Entertainment World Mourns the ‘Dreamer’ Director David Lynch
Lynch’s death inspired tributes from fellow filmmakers, celebrities and past collaborators, who praised his visionary work and singular voice.
www.nytimes.com
January 16, 2025 at 10:47 PM
The death of the surrealist film and television director David Lynch inspired tributes from fellow filmmakers, celebrities and past collaborators, who praised his visionary work and singular voice.
Reposted by Amit Sud
Massively parallel reporter assays (MPRAs) testing >680,000 sequences combined with machine learning to improve regulatory element & variant effect prediction. Amazing work by @vagar.bsky.social, Fumitaka Inoue, @jshendure.bsky.social and many others as part of ENCODE.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Massively parallel characterization of transcriptional regulatory elements - Nature
Lentivirus-based reporter assays for 680,000 regulatory sequences from three cell lines coupled to machine-learning models lead to insights into the grammar of cis-regulatory elements.
www.nature.com
January 15, 2025 at 5:05 PM
Massively parallel reporter assays (MPRAs) testing >680,000 sequences combined with machine learning to improve regulatory element & variant effect prediction. Amazing work by @vagar.bsky.social, Fumitaka Inoue, @jshendure.bsky.social and many others as part of ENCODE.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Amit Sud
I've written a lot about polygenic risk scores in DNA testing, which, for at least the time being, are regarded as largely unhelpful (at best). That's because these tests analyze many genes to predict risk of a condition. With our current knowledge of the genome, that's just tough to do.
January 15, 2025 at 8:22 PM
I've written a lot about polygenic risk scores in DNA testing, which, for at least the time being, are regarded as largely unhelpful (at best). That's because these tests analyze many genes to predict risk of a condition. With our current knowledge of the genome, that's just tough to do.
Reposted by Amit Sud
In science, we often see weird blips in the data. The question: is it artefact (usually!), or something new & exciting? We don’t always have time to dig deep.
Our paper in @nature.com today came from just such a blip. So don’t ignore the weird stuff. Pull on that thread...
Our paper in @nature.com today came from just such a blip. So don’t ignore the weird stuff. Pull on that thread...
January 15, 2025 at 9:44 PM
In science, we often see weird blips in the data. The question: is it artefact (usually!), or something new & exciting? We don’t always have time to dig deep.
Our paper in @nature.com today came from just such a blip. So don’t ignore the weird stuff. Pull on that thread...
Our paper in @nature.com today came from just such a blip. So don’t ignore the weird stuff. Pull on that thread...
Reposted by Amit Sud
Osteosarcoma, an aggressive bone cancer, most commonly affects children and young adults.
New research solves the mystery of what drives the genomic rearrangements causing the aggressive development and evolution of osteosarcoma tumours.
www.ebi.ac.uk/about/news/r...
🧪
New research solves the mystery of what drives the genomic rearrangements causing the aggressive development and evolution of osteosarcoma tumours.
www.ebi.ac.uk/about/news/r...
🧪
Researchers uncover what drives aggressive bone cancer
Study identifies a novel mechanism driving osteosarcoma and provides insights to help predict patient outcomes.
www.ebi.ac.uk
January 14, 2025 at 4:13 PM
Osteosarcoma, an aggressive bone cancer, most commonly affects children and young adults.
New research solves the mystery of what drives the genomic rearrangements causing the aggressive development and evolution of osteosarcoma tumours.
www.ebi.ac.uk/about/news/r...
🧪
New research solves the mystery of what drives the genomic rearrangements causing the aggressive development and evolution of osteosarcoma tumours.
www.ebi.ac.uk/about/news/r...
🧪
Reposted by Amit Sud
Reposted by Amit Sud
We held a great launch meeting at @cpmoxford.bsky.social last week for our award from #RHO to research health #inequalities and #ethnicity in the NHS genomic medicine service. Great discussions from @medesh.bsky.social @bughayleyw.pharmsky.app and many others [apols 4 ltd knowledge bsk addrs] 1/8
January 12, 2025 at 4:13 PM
We held a great launch meeting at @cpmoxford.bsky.social last week for our award from #RHO to research health #inequalities and #ethnicity in the NHS genomic medicine service. Great discussions from @medesh.bsky.social @bughayleyw.pharmsky.app and many others [apols 4 ltd knowledge bsk addrs] 1/8
Reposted by Amit Sud
Happy New Year! (and first post here 😀) Excited to share the final version of our work where we combine deep mutational scanning, cryo-EM, and molecular dynamics to further resolve the mechanisms of pH sensing in GPCRs.
🧵(1/n)
www.cell.com/cell/fulltex...
🧵(1/n)
www.cell.com/cell/fulltex...
January 6, 2025 at 7:57 PM
Happy New Year! (and first post here 😀) Excited to share the final version of our work where we combine deep mutational scanning, cryo-EM, and molecular dynamics to further resolve the mechanisms of pH sensing in GPCRs.
🧵(1/n)
www.cell.com/cell/fulltex...
🧵(1/n)
www.cell.com/cell/fulltex...
Reposted by Amit Sud
BBC Radio4 is celebrating a hundred years of the Shipping Forecast this New Year’s Day - as loyal listeners, here’s our contribution damonandnaomi.bandcamp.com/track/sailin...
Sailing By, by Damon & Naomi
from the album A Sky Record
damonandnaomi.bandcamp.com
December 31, 2024 at 11:28 PM
BBC Radio4 is celebrating a hundred years of the Shipping Forecast this New Year’s Day - as loyal listeners, here’s our contribution damonandnaomi.bandcamp.com/track/sailin...
Reposted by Amit Sud
From @nytopinion.nytimes.com
Jimmy Carter “described his second career as ‘waging peace.’ That work remains far from finished, and it remains for those who admired Mr. Carter to continue,” the editorial board writes.
Jimmy Carter “described his second career as ‘waging peace.’ That work remains far from finished, and it remains for those who admired Mr. Carter to continue,” the editorial board writes.
Opinion | America Needs More Jimmy Carters
He was a model ex-president and achieved a great deal in office.
nyti.ms
December 29, 2024 at 11:28 PM
From @nytopinion.nytimes.com
Jimmy Carter “described his second career as ‘waging peace.’ That work remains far from finished, and it remains for those who admired Mr. Carter to continue,” the editorial board writes.
Jimmy Carter “described his second career as ‘waging peace.’ That work remains far from finished, and it remains for those who admired Mr. Carter to continue,” the editorial board writes.
Reposted by Amit Sud
Our final paper of 2024 is a great collaborative effort between multiple genome stability groups (Steve Roberts & David Cortez). Kudos to the extremely talented scientists - @tmweaver.bsky.social @k4v1.bsky.social, Justin Ling, and Cameron Cordero.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Contributing factors to the oxidation-induced mutational landscape in human cells - Nature Communications
8-oxoG is a common single-base DNA lesion caused by oxidative stress. Here, authors characterize the mutational signature of potassium bromate (KBrO3) exposure, the chromatin structural determinants o...
www.nature.com
December 24, 2024 at 1:59 PM
Our final paper of 2024 is a great collaborative effort between multiple genome stability groups (Steve Roberts & David Cortez). Kudos to the extremely talented scientists - @tmweaver.bsky.social @k4v1.bsky.social, Justin Ling, and Cameron Cordero.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Amit Sud
I'm going to repost a #thread here about a recent #paper from my group together with the labs of Marketa Tomkova and Skirmantas Kriaucionis:
nature.com/articles/s41588-024-01945-x
In it, we show that epigenetic DNA methylation causes errors during DNA replication!
#epigenetics #mutations
1/🧵
nature.com/articles/s41588-024-01945-x
In it, we show that epigenetic DNA methylation causes errors during DNA replication!
#epigenetics #mutations
1/🧵
Human DNA polymerase ε is a source of C>T mutations at CpG dinucleotides - Nature Genetics
A new method called polymerase error rate sequencing (PER-seq) can measure the nucleotide misincorporation rate of DNA polymerases. DNA polymerase ε mutants produce an excess of CpG<TpG errors duri...
nature.com
December 2, 2024 at 12:12 PM
I'm going to repost a #thread here about a recent #paper from my group together with the labs of Marketa Tomkova and Skirmantas Kriaucionis:
nature.com/articles/s41588-024-01945-x
In it, we show that epigenetic DNA methylation causes errors during DNA replication!
#epigenetics #mutations
1/🧵
nature.com/articles/s41588-024-01945-x
In it, we show that epigenetic DNA methylation causes errors during DNA replication!
#epigenetics #mutations
1/🧵
Reposted by Amit Sud
This work finds that costly foundation models are outperformed by CNNs in genomics benchmarks, and are outperformed by *linear* autoregression in time-series benchmarks. 👀
Specialized Foundation Models Struggle to Beat Supervised Baselines
Following its success for vision and text, the "foundation model" (FM) paradigm -- pretraining large models on massive data, then fine-tuning on target tasks -- has rapidly expanded to domains in the ...
arxiv.org
December 12, 2024 at 7:26 AM
This work finds that costly foundation models are outperformed by CNNs in genomics benchmarks, and are outperformed by *linear* autoregression in time-series benchmarks. 👀