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...

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

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...

One of the greats of 20th century biology. What a life. www.youtube.com/watch?v=v9Em...

This looks like a creative use of transformers. Looking forward to diving into this. arxiv.org/abs/2508.04111

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.

#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!

This week's genome editing triumph is a big deal. Here's why erictopol.substack.com/p/the-first-...

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…”

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.

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... 🧵

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!)

+1 Anshul Part of this means reviewers not ripping on manuscripts that explicitly mention limitations *for those limitations*

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.

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/...

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...

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.

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...

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.

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)

📣 New from @ryandhindsa.bsky.social & co! 📄Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes

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...

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.

⚡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...

📢 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...

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

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 🧵

✨ 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

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.

How population stratification makes environments look like genes. A short 🧵:

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/

I don’t! Likely it would look a lot like normal Luria-Delbruck since the relative rate of spacer acquisition is significantly lower than receptor modifications. But Manoshi Datta and Roy Kishony have a great perspective piece on this from 2018: www.nature.com/articles/d41...

Friends and colleagues, I’ve written a book on effective functional genomics study design, which will be available on Amazon in a couple of weeks. Sharing the TOC to spark interest. I hope students and those planning genomics experiments will find it useful! I’ll share updates soon

New pre-print alert 🚨 Interested in what @ikafetzo.bsky.social learned about DNA hypomethylation in cancer from investigating surprising gains DNA methylation in DNMT1 KO cells? Read all about it here: www.biorxiv.org/content/10.1... For a quick summary see this 🧵 1/8 #epigenetics

What if one variant can cause splicing outliers transcriptome-wide? In our preprint, we show how examining transcriptome-wide patterns of splicing outliers can both diagnose individuals with rare spliceopathies and uncover novel disease-gene relationships! (www.medrxiv.org/content/10.1...)

Very excited to announce that the single cell/nuc. RNA/ATAC/multi-ome resource from ENCODE4 is now officially public. This includes raw data, processed data, annotations and pseudobulk products. Covers many human & mouse tissues. 1/ www.encodeproject.org/single-cell/...

Excited to share our preprint: Cohort-level analysis of human de novo mutations points to drivers of clonal expansion in spermatogonia! We developed methods to uncover drivers of clonal expansions in sperm (CES) using 55k disease trios & gnomAD SNV data. www.medrxiv.org/content/10.1...

It is that time of the year again when @odedrechavi.bsky.social and I do our annual “your favorite paper of the year” thread. Now only on Bluesky! Please link to your favorite paper in the comments and say a few words why you loved it so much. Happy holidays and happy reading!

Very nice study showing that deep intronic variants causing cryptic exon inclusions may be a more common cause of rare genetic disorders than previously appreciated.

Very interesting paper by Philipp Voigt about nucleosomal asymmetry at bivalent domains. "Bivalency recruits H3K27me3 but not H3K4me3 readers, promoting a poised state" www.cell.com/molecular-ce...

Brief thread on our opinion article "Q-rich activation domains: flexible ‘rulers’ for transcription start site selection?". Transcription people are surely aware of the important reports on the DNA sequence determinants of start site (TSS) selection in the human genome that came out this year. 1/15

What topics are better taught starting from the more complex (but more representative) concept first and then going back to simple models? My example is teaching polygenic models of disease first, but can be outside genetics.

Our ChromBPNet preprint out! www.biorxiv.org/content/10.1... Huge congrats to Anusri! This was quite a slog (for both of us) but we r very proud of this one! It is a long read but worth it IMHO. Methods r in the supp. materials. Bluetorial coming soon below 1/

Been looking forward to sharing this for a long time! Great collaboration with folks from across the world in which we identified a SVA_E insertion missed by standard clinical testing in individuals with Canavan disease, an early onset neurodegenerative disease. www.medrxiv.org/content/10.1...

🚨 Excited to announce the Marker paper for the GREGoR Consortium! arxiv.org/abs/2412.14338 Accelerating #RareDisease diagnostics with cutting-edge #Genomics and global data sharing of omics and deep phenotyping from ~7500 individuals on NHGRI AnVIL and much more to come! 🧬

What do GWAS and rare variant burden tests discover, and why? Do these studies find the most IMPORTANT genes? If not, how DO they rank genes? Here we present a surprising result: these studies actually test for SPECIFICITY! A 🧵on what this means... (🧪🧬) www.biorxiv.org/content/10.1...

And here is my condensed guide on how to science: top 5 Rules

Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of @jonmarkert.bsky.social! tinyurl.com/setd2