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Leandros Boukas

@leandrosboukas.bsky.social
160 followers 273 following 39 posts

Epigenetics/Gene regulation, Human Genetics, Population Genetics. Medical Genetics & Genomics Fellow at Harvard Medical School and Boston Children's Hospital. MD, PhD

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Reposted by Leandros Boukas
American Society of Human Genetics (ASHG) @geneticssociety.bsky.social · 04/09/2026
@ajhgnews.bsky.social sat with Kimberley Anderson, PhD, in the latest "Inside AJHG" to discuss her recently published paper, “Androgens mediate sexual dimorphism in Pilarowski-Bjornsson syndrome.” ➡️ bit.ly/4hbuxsp #ASHG #HumanGenetics #GeneticsDiscoveries
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Jesse Engreitz @jengreitz.bsky.social · 04/08/2026
Update: scE2G is now online at Nature Genetics! Since the preprint, we added a new benchmark on a fully held-out CRISPR dataset. scE2G continues to show state-of-the-art performance, reinforcing that it generalizes well nature.com/articles/s41588-026-02695-8 1/
Held-out CRISPR benchmark: n=189 positives, 4,175 tested pairs from 5 cell types. Weighted AUPRC bar chart with scE2G-Multiome and scE2G-ATAC highest, above Distance to TSS, ABC, and 8 other single-cell methods.
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Leandros Boukas @leandrosboukas.bsky.social · 16/07/2026
Together with Hans Bjornsson (and @kasperdhansen.bsky.social, and others) we have spent many years thinking about the molecular basis of Mendelian disorders caused by variants in chromatin regulators. We have written a review where we discuss our thoughts: www.tandfonline.com/doi/full/10....
tandfonline.com
Mendelian disorders of the epigenetic machinery: a decade of insights into the molecular basis
The Mendelian disorders of the Epigenetic Machinery (MDEMs), or Chromatinopathies, are now understood to be a collectively common cause of childhood neurodevelopmental delays and intellectual disab...
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Craig Kaplan @triggerloop.bsky.social · 15/05/2026
Pleased to talk about two related papers from our lab this Spring in GENETICS @genetics-gsa.bsky.social. These two studies are each the work of graduate students in my lab, with contributions from our colleagues. I will describe our system first and then each of the studies /1
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Wendy Bickmore @wbickmor.bsky.social · 08/05/2026
Although cohesin-sensitive, long-range enhancer activation is equivalent in nature to proximal activation. Cooperativity can arise from different levels of activation inputs operating on a non-linear response function. @eliasfriman.bsky.social @uoe-igc.bsky.social www.biorxiv.org/content/10.6...
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Jason Moore @moorejh.bsky.social · 21/04/2026
definitely not AI generated
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Michela Palamin @mpalamin.bsky.social · 24/03/2026
ChromSMF preprint is out!🚀 tinyurl.com/ChromSMF We often piece together chromatin regulation layer by layer from separate assays. But this can be limiting! In @arnaudkr.bsky.social's lab, we developed a method to directly study multiple layers on the same DNA molecule! 🧬 What does this unlock? ⬇️
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Aaron Quinlan (he/him) @aaronquinlan.bsky.social · 12/03/2026
In collab w @hdashnow.bsky.social, we have a new preprint out on tandem repeat (TR) mutagenesis! Using HiFi sequencing, we profiled nearly 8 million TR loci across four generations of a large CEPH/Utah family and identified 1,270 de novo expansions and contractions. www.biorxiv.org/content/10.6...
biorxiv.org
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Leandros Boukas @leandrosboukas.bsky.social · 05/03/2026
Very happy to share our work with Seth Berger and UCI-GREGoR at @ajhgnews.bsky.social . We developed and extensively evaluated a method - duoNovo - that uses long-read sequencing to detect de novo variants using *only one* biological parent. (1/n) R package: github.com/sbergercnmc/...
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John Greally @greally.bsky.social · 01/03/2026
A reminder that we are actively recruiting a geneticist to the Department of Genetics at Albert Einstein College of Medicine careers-einstein.icims.com/jobs/17847/a...
careers-einstein.icims.com
Einstein
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Leandros Boukas @leandrosboukas.bsky.social · 01/03/2026
Sad to hear of David Botstein's passing. I got into Genomics after attending the famous Bar Harbor course at Jackson Labs in 2013. Botstein was the senior lecturer that year. He had an incredible presence throughout those two weeks, (1/n)
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noahconnally.bsky.social @noahconnally.bsky.social · 05/02/2026
A new preprint out with Shamil Sunyaev. We talk about GWAS, gene expression, evolution, and why searching for trait-associated eQTLs is easier in cattle and pigs. www.biorxiv.org/content/10.6...
biorxiv.org
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John Greally @greally.bsky.social · 05/02/2026
Please share this with your network: Postdoctoral position available in my group. www.linkedin.com/jobs/view/43...
linkedin.com
Albert Einstein College of Medicine hiring Postdoctoral position studying functional non-coding variants in neurodevelopmental disorders, Bronx, New York City, USA c in New York City Metropolitan Area...
Posted 9:40:20 PM. A postdoctoral fellow position is open with 2 years of funding from the Simons Foundation Autism…See this and similar jobs on LinkedIn.
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Arnaud Krebs @arnaudkr.bsky.social · 12/01/2026
Very important work to reconcile canonical transcription initiation structures with the promoter diversity occurring in vivo. Some explanation on how the large majority of our promoters (TATA-less) ma initiate transcription through contacts downstream of the TSS.
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Rob Klose @robklose.bsky.social · 11/12/2025
An early Christmas present for those interested in chromatin and transcription! Fantastic work from @au-ho-yu.bsky.social and @aleksszczurek.bsky.social . Thanks to Inge and Michiel for their help. Please repost! www.biorxiv.org/content/10.6...
biorxiv.org
SET1/MLL complexes control transcription independently of H3K4me3
Histone H3 lysine 4 trimethylation (H3K4me3) at gene promoters is thought to play a central role in gene transcription. H3K4 methylation is deposited by the SET1 (A/B) and MLL (1-4) multi-protein comp...
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Sasha Gusev @sashagusevposts.bsky.social · 30/11/2025
Massive single-cell study by Kanai et al (www.medrxiv.org/content/10.1...): - Once statistical power is high, constrained genes have more (though weaker) eQTLs. - Chromatin-QTLs near constrained genes have "normal" effect sizes, colocalize more with disease, but exhibit attenuated peak-gene effects.
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FragileNucleosome @fnucleosome.bsky.social · 24/11/2025
Do you have an exciting new chromatin/transcription story that you'd like to share with the #FN community? Fill out this form to be considered for a talk in our Jan-June 2026 schedule! forms.gle/TBi38UgYxPAB... Please repost and share!
forms.gle
Application to speak in the Fragile Nucleosome series
Thank you for your interest in our seminar series! We use a variety of different session formats but, in general, trainees can plan for a ~15 min talk + 5min Q/A and PIs can plan for a ~25min talk +...
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Michael Love @mikelove.bsky.social · 18/08/2025
Excited to share this preprint from first author Jon Rosen, a postdoctoral fellow in the @klmohlke.bsky.social lab and my lab. We examine eQTL study sample size and how this affects signal discovery and rates of colocalization with GWAS. www.biorxiv.org/content/10.1...
biorxiv.org
Higher eQTL power reveals signals that boost GWAS colocalization
Expression quantitative trait locus (eQTL) studies in human cohorts typically detect at least one regulatory signal per gene, and have been proposed as a way to explain mechanisms of genetic liability...
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John Greally @greally.bsky.social · 21/10/2025
It's publication day, and Cold Spring Harbor Laboratory Press is running a promotion bundling the hard cover and e-book, and other offers: cshlpress.com/default.tpl?... #EpigeneticsBook
cshlpress.com
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Leandros Boukas @leandrosboukas.bsky.social · 11/10/2025
Looking forward to presenting duoNovo at ASHG this week. We use long-read sequencing to detect de novo variants without having to sequence both parents. It's conceptually straightforward, and performs very accurately among variants likely to be clinically relevant. www.medrxiv.org/content/10.1...
medrxiv.org
Identification of de novo variants from parent-proband duos via long-read sequencing
While de novo variants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available,...
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Leandros Boukas @leandrosboukas.bsky.social · 08/09/2025
One of the greats of 20th century biology. What a life. www.youtube.com/watch?v=v9Em...
youtube.com
David Baltimore
YouTube video by InfiniteHistoryProject MIT
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Leandros Boukas @leandrosboukas.bsky.social · 08/08/2025
This looks like a creative use of transformers. Looking forward to diving into this. arxiv.org/abs/2508.04111
arxiv.org
Negative binomial regression and inference using a pre-trained transformer
Negative binomial regression is essential for analyzing over-dispersed count data in in comparative studies, but parameter estimation becomes computationally challenging in large screens requiring mil...
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John Greally @greally.bsky.social · 02/08/2025
My book Epigenetics: History, Molecules and Diseases will be published in exactly one month (September 2). Finalizing cover (looks great), probably going to printer this week. Nervous anticipation is the mood right now.
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Annemieke Aartsma-Rus @oligogirl.bsky.social · 27/05/2025
#apaperaday is back from holiday. Yuzu is still with the birbsitter so a holiday picture it is. Today's pick is from @nejm.org by Musunuru et al on an N=1 case (patient with severe metabolic disease) treated by base editing (CRISPR therapy). DOI: 10.1056/NEJMoa2504747 Very good way to restart!
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Eric Topol @erictopol.bsky.social · 18/05/2025
This week's genome editing triumph is a big deal. Here's why erictopol.substack.com/p/the-first-...
Multiple headlines about the first CRISPR 2.0 personalized genome editing and photo of the baby treated
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Richard Sever @richardsever.bsky.social · 18/05/2025
Reminded of Ed Yong’s response to this question: “If I cover a preprint, I talk to 2-3 experts to get their views before writing the story. That’s exactly what I do if I cover a journal article…”
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Leandros Boukas @leandrosboukas.bsky.social · 16/05/2025
Looking forward to this next week
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Leandros Boukas @leandrosboukas.bsky.social · 09/05/2025
Beautiful combination of population-scale genetic analyses and mouse work. Damaging variants in a highly constrained chromatin remodeler (CHD1) are better tolerated in males, with mouse experiments indicating a protective effect of androgens.
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Lars Velten @larsplus.bsky.social · 08/05/2025
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... 🧵
cell.com
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...
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Jeff Leek @jtleek.bsky.social · 30/04/2025
Check this out - the company I co-founded is trying to figure out how to make this super easy product.synthesize.bio (and we have beta models out to AI generate new expression data based on experimental design!)
product.synthesize.bio
Bioinformatics Platform | NGS Data Analysis - Synthesize BioArrow Right
Experience a next-gen analysis tool tailored for biology · Enhance discovery with our dynamic visualization canvas · A central space for bioinformatics teamwork.
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Michael Love @mikelove.bsky.social · 08/04/2025
+1 Anshul Part of this means reviewers not ripping on manuscripts that explicitly mention limitations *for those limitations*
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Anshul Kundaje @anshulkundaje.bsky.social · 08/04/2025
Just a gentle reminder that deceptive hyping in scientific publications (which includes preprints) is actually antithetical to the core mission of the scientific process. We can stay grounded, truthful, humble while being ambitious. Revealing caveats, pitfalls & limitations speeds up progress.
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Gang Fang @gangfang.bsky.social · 30/03/2025
Great new review @natrevgenet.bsky.social by @sedlazeck.bsky.social @timp0.bsky.social and @yileifu.bsky.social! 👇highlighting both the promise of long read DNA methylation analysis and remaining challenges such as the difficulty to benchmark 5hmC and non-CG 5mC given their low abundance👏
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Leandros Boukas @leandrosboukas.bsky.social · 24/03/2025
This is really a fantastic piece on causality in biological systems, and relevant beyond neuroscience onlinelibrary.wiley.com/doi/10.1111/...
onlinelibrary.wiley.com
Beyond Mechanism—Extending Our Concepts of Causation in Neuroscience
The search for neural mechanisms of behaviour often relies on a synchronic, driving view of causation, where neural activity drives more neural activity, which eventually drives behaviour. The real c...
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Stefan Schoenfelder @stefanschoenfelder.bsky.social · 21/03/2025
Plenty of work required to rigorously test the proposed hypothesis but my initial thoughts are this perspective by Adrian Bird in @cp-molcell.bsky.social may well be the most significant conceptual advance in the 3D genome organisation field in years: www.sciencedirect.com/science/arti...
sciencedirect.com
Cohesin as an essential disruptor of chromosome organization
Cohesin is a multi-subunit molecular machine that is able to create lateral chromatin loops within a linear chromosome fiber. Despite intense study, a…
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Tuuli Lappalainen @tuuliel.bsky.social · 19/03/2025
I just the word epigenetics; it has so many meanings that it's next to useless. I prefer less ambigous terms: Epigenomic data for chromatin-related data (including methylation); gene regulatory mechanisms for the general phenomenon of how genes are regulated, etc.
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Nikolai Slavov @slavov-n.bsky.social · 01/03/2025
Remember the role of regulation by degradation. Research often focusses on the regulation of synthesis rates. Here, @andrewleduc.bsky.social and I show that degradation can be just as influential in shaping protein abundance variation. www.biorxiv.org/content/10.1...
biorxiv.org
Protein degradation and growth dependent dilution substantially shape mammalian proteomes
Cellular protein concentrations are maintained through a balance of synthesis and clearance. Clearance occurs through both protein degradation and growth-dependent dilution. At slow growth, clearance ...
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Wolfgang Huber @wkhuber.bsky.social · 27/02/2025
The analogy of omics data normalization and cooking: some processing is usually necessary, overcooking makes it bland, highly over-processed foods are unhealthy, and the quality of the ingredients matters.
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Leandros Boukas @leandrosboukas.bsky.social · 27/02/2025
I'm very happy to share our latest work with Seth Berger and the UCI-GREGoR team. Using long-read sequencing, we can detect de novo variants *without* sequencing both parents. We call our method duoNovo. preprint: www.medrxiv.org/content/10.1... R package: github.com/sbergercnmc/... (1/n)
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The American Journal of Human Genetics @ajhgnews.bsky.social · 26/02/2025
📣 New from @ryandhindsa.bsky.social & co! 📄Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes
cell.com
Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes
Thousands of neurodevelopmental disorder (NDD)-associated genes remain undiscovered, limiting genetic diagnoses. Here, we employ inheritance-specific machine learning models, incorporating gene expres...
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Sasha Gusev @sashagusevposts.bsky.social · 26/02/2025
We finally have some well-powered whole-genome heritability estimates, including a quasi-behavioral trait (BMI). For height, ~89% of the heritability estimated to reside in common variants. For BMI and WHR, ~100% estimated in common variants. www.biorxiv.org/content/10.1...
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Leandros Boukas @leandrosboukas.bsky.social · 24/02/2025
Really excited to present in this fantastic seminar series this Wednesday. Will be sharing some of the insights we have gained into disease-associated epigenetic changes by studying the Mendelian developmental disorders of the epigenetic machinery.
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FragileNucleosome @fnucleosome.bsky.social · 06/02/2025
⚡Next #FragileNucleosome meeting is less than a week away! Three amazing ECR scientists, 🔬@anajaneva.bsky.social, 🧠@anastasiahains.bsky.social, & 🧬@martyyang.bsky.social will discuss their research next Wed! 🗓️Don't forget to register: us06web.zoom.us/webinar/regi...
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Sarah Marzi @sj-marzi.bsky.social · 30/01/2025
📢 CUT&Tag version 3 Sometimes the preprint to paper route can be quite the odyssey. And so in that vein, we are delighted to give you version 3 of our CUT&Tag optimization and benchmarking manuscript: www.biorxiv.org/content/10.1...
biorxiv.org
CUT&Tag recovers up to half of ENCODE ChIP-seq histone acetylation peaks
Techniques for genome-wide epigenetic profiling have been undergoing accelerated development toward recovery of high-quality data from bulk and single cell samples. DNA-protein interactions have tradi...
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Jeremy Berg @jeremymberg.bsky.social · 26/01/2025
Let me give a concrete example of the importance of applications with high risk-high reward as well as the role of NIH staff in taking risks. Decades ago, a physical chemist proposed ideas about doing mass spectrometry on proteins (when this was deemed probably impossible). 1/n
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Jonathan Pritchard @jkpritch.bsky.social · 26/01/2025
Modern GWAS can identify 1000s of significant hits but it can be hard to turn this into biological insight. What key cellular functions link genetic variation to disease? I'm very excited to present our new work combining associations and Perturb-seq to build interpretable causal graphs! A 🧵
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Meghana Oak @meghana-oak.bsky.social · 22/01/2025
✨ Excited to share my latest preprint on how H3K4 methylation promotes transcriptional memory from gametes to embryos across a transcriptionally silent window — crucial for proper zygotic genome activation and development. 🐸🧬✨ 📄 Check it out here:
doi.org/10.1101/2025... 👇 Highlights below
doi.org
H3K4 methylation-promoted transcriptional memory ensures faithful zygotic genome activation and embryonic development
In the life of a vertebrate embryo, gene expression is initiated for the first time at zygotic genome activation (ZGA). Maternally expressed transcription factors present in the embryo are essential f...
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Leandros Boukas @leandrosboukas.bsky.social · 22/01/2025
Very interesting study/thread. It's not widely appreciated that it's not only transcription factors that provide location specificity to chromatin modifiers. The CxxC domain binds unmethylated CpGs --> directs binding to CpG islands. No interaction with TFs - or even active transcription - needed.
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Sasha Gusev @sashagusevposts.bsky.social · 20/01/2025
How population stratification makes environments look like genes. A short 🧵:
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Anshul Kundaje @anshulkundaje.bsky.social · 17/01/2025
We share a lot of our ideas, code, datasets (that we spend years sanitizing) early. Often way before we release preprints. We do this so that others can use, build on, improve & even "beat" our approaches. But I want to say a few things about some simple expectations 1/
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