Leandros Boukas
@leandrosboukas.bsky.social
Epigenetics/Gene regulation, Human Genetics, Population Genetics. Medical Genetics & Genomics Fellow at Harvard Medical School and Boston Children's Hospital. MD, PhD
Reposted by Leandros Boukas
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...
www.biorxiv.org/content/10.1...
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...
www.biorxiv.org
August 18, 2025 at 12:18 PM
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...
www.biorxiv.org/content/10.1...
Reposted by Leandros Boukas
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/default.tpl?...
#EpigeneticsBook
October 21, 2025 at 3:18 PM
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/default.tpl?...
#EpigeneticsBook
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...
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...
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,...
www.medrxiv.org
October 11, 2025 at 7:33 PM
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...
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...
David Baltimore
YouTube video by InfiniteHistoryProject MIT
www.youtube.com
September 8, 2025 at 6:21 PM
This looks like a creative use of transformers. Looking forward to diving into this.
arxiv.org/abs/2508.04111
arxiv.org/abs/2508.04111
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...
arxiv.org
August 7, 2025 at 11:44 PM
This looks like a creative use of transformers. Looking forward to diving into this.
arxiv.org/abs/2508.04111
arxiv.org/abs/2508.04111
Reposted by Leandros Boukas
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.
Finalizing cover (looks great), probably going to printer this week.
Nervous anticipation is the mood right now.
August 2, 2025 at 8:48 PM
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.
Finalizing cover (looks great), probably going to printer this week.
Nervous anticipation is the mood right now.
Reposted by Leandros Boukas
#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!
May 27, 2025 at 4:35 AM
#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!
Reposted by Leandros Boukas
May 18, 2025 at 2:37 PM
Reposted by Leandros Boukas
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…”
“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…”
Absolutely.
Preprints are for communicating among scientists.
If a journalist wants to cover one, they should commission a peer review.
Preprints are for communicating among scientists.
If a journalist wants to cover one, they should commission a peer review.
Resolved: preprints should not be covered in the news, no matter how tantalizing the results are
May 18, 2025 at 12:59 PM
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…”
“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…”
Looking forward to this next week
Join us on Wednesday next week for two exciting talks on transcription regulation from @kasitc.bsky.social and @davidsuter.bsky.social!
You can register at: us06web.zoom.us/webinar/regi...
You can register at: us06web.zoom.us/webinar/regi...
May 16, 2025 at 9:46 AM
Looking forward to this next week
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.
Androgens mediate sexual dimorphism in Pilarowski-Bjornsson Syndrome https://www.medrxiv.org/content/10.1101/2025.05.06.25326635v1
May 9, 2025 at 1:37 AM
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.
Reposted by Leandros Boukas
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 Leandros Boukas
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!)
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.
product.synthesize.bio
April 30, 2025 at 5:19 PM
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!)
Reposted by Leandros Boukas
+1 Anshul
Part of this means reviewers not ripping on manuscripts that explicitly mention limitations *for those limitations*
Part of this means reviewers not ripping on manuscripts that explicitly mention limitations *for those limitations*
April 8, 2025 at 1:22 PM
+1 Anshul
Part of this means reviewers not ripping on manuscripts that explicitly mention limitations *for those limitations*
Part of this means reviewers not ripping on manuscripts that explicitly mention limitations *for those limitations*
Reposted by Leandros Boukas
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.
April 8, 2025 at 9:03 AM
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.
Reposted by Leandros Boukas
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👏
We summarized state-of-the-art computational methods for DNA methylation analysis using long-read sequencing, covering everything from base calling to sample-level, cell-type-level, and even population-scale analysis. Huge thanks to @sedlazeck.bsky.social and @timp0.bsky.social for this great work!
New online! Computational analysis of DNA methylation from long-read sequencing
March 30, 2025 at 8:56 PM
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👏
This is really a fantastic piece on causality in biological systems, and relevant beyond neuroscience
onlinelibrary.wiley.com/doi/10.1111/...
onlinelibrary.wiley.com/doi/10.1111/...
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...
onlinelibrary.wiley.com
March 24, 2025 at 10:41 PM
This is really a fantastic piece on causality in biological systems, and relevant beyond neuroscience
onlinelibrary.wiley.com/doi/10.1111/...
onlinelibrary.wiley.com/doi/10.1111/...
Reposted by Leandros Boukas
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...
www.sciencedirect.com/science/arti...
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…
www.sciencedirect.com
March 21, 2025 at 11:19 PM
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...
www.sciencedirect.com/science/arti...
Reposted by Leandros Boukas
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.
March 19, 2025 at 10:29 AM
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.
Reposted by Leandros Boukas
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...
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...
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 ...
www.biorxiv.org
March 1, 2025 at 2:08 PM
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...
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...
Reposted by Leandros Boukas
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.
some processing is usually necessary, overcooking makes it bland, highly over-processed foods are unhealthy, and the quality of the ingredients matters.
February 27, 2025 at 8:01 AM
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.
some processing is usually necessary, overcooking makes it bland, highly over-processed foods are unhealthy, and the quality of the ingredients matters.
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)
preprint: www.medrxiv.org/content/10.1...
R package: github.com/sbergercnmc/...
(1/n)
February 27, 2025 at 10:49 PM
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)
preprint: www.medrxiv.org/content/10.1...
R package: github.com/sbergercnmc/...
(1/n)
Reposted by Leandros Boukas
📣 New from @ryandhindsa.bsky.social & co!
📄Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes
📄Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes
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...
www.cell.com
February 26, 2025 at 6:08 PM
📣 New from @ryandhindsa.bsky.social & co!
📄Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes
📄Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes
Reposted by Leandros Boukas
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...
www.biorxiv.org/content/10.1...
February 26, 2025 at 6:25 PM
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...
www.biorxiv.org/content/10.1...
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.
‼️ This Wednesday! Don’t forget to register as we host three amazing ECR scientists!
@manucazottes.bsky.social @robertadolling1.bsky.social
@leandrosboukas.bsky.social
⚡️Our recurring registration link:
us06web.zoom.us/webinar/regi...
@manucazottes.bsky.social @robertadolling1.bsky.social
@leandrosboukas.bsky.social
⚡️Our recurring registration link:
us06web.zoom.us/webinar/regi...
February 24, 2025 at 12:40 AM
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.