Congrats also to
@JofanChien
, Alexey Kozlenkov, Junhao Li, Chunyu Liu and all our collaborators

Big congrats to first author
@HengXu4
(soon to be on the postdoc market!) for leading this huge effort, which was another great collaboration with
@DrachevaStella
and part of the
@NIMHgov
PsychENCODE project. Read all about it here:

biorxiv.org/content/10.6...

Our browser built on igv.js with a customized track selector makes the DNA methylome, RNA, and ChIP-seq data accessible for fast viewing and analysis:

brainome.ucsd.edu/BrainHydroxy...

Finally, our analyses pinpointed cis regulatory elements (CREs) where developmental changes in DNA methylation are tightly linked with histone modifications and RNA expression. Some of these relationships were distinct in excitatory vs. inhibitory neurons

Large sex differences in 5hmC throughout the X chromosome, reflecting a role for 5hmC in female X inactivation and escape from X-inactivation

three kitsch cat clocks are lined up on a white wall ALT: three kitsch cat clocks are lined up on a white wall

TET-mediated conversion of 5mC to 5hmC is impacted by transcription throughout the lifespan in a reliable, clock-like fashion. We also found...

There were some fascinating surprises, including a new kind of DNA Methylation Clock based on strand asymmetry in 5hmC. We believe the linear increase in the difference in 5hmC between the sense and antisense strands in highly expressed genes shows that...

We found a dramatic, genome-wide conversion of nearly half of all genomic 5mC to 5hmC, unfolding over the first 10-20 years of life, in both excitatory and inhibitory neurons

We collected and analyzed a new dataset, with BS and OxBS-seq as well as ChIP- and RNA-Seq from the PFC in 103 donors, aged 3 months to 77 years

Diagram of cyclic interconversion of cytosine to methylcytosine to hydroxymethylcytosine and back to C

Neurons are enriched in 5-hydroxy-methyl-cytosine (5hmC), the hidden underside of DNA methylation which is not distinguished from 5mC in conventional bisulfite sequencing data.

The DNA methylome is an incredibly rich signature of cell identity and gene regulation. But what if we're missing half the story? Our new preprint shows that, for neurons, 5-methyl-cytosine (5mC) is only the tip of the methylberg... 🧵

BICAN: A cell census of the developing human brain Building on their landmark efforts to create cell-type atlases of adult brains using single-cell and spatial genomics technologies, researchers in the BRAIN ...

Exciting to see a package of brain development studies (mainly from mouse) from the NIH (not on bsky!?) #BRAINInitiative . Congrats to the authors, and I'm looking forward to digging into the findings/data.

www.nature.com/collections/...

What do you get when you cross a joke with a rhetorical question?

Thank you for clearly articulating what's needed. Scientists need to have the courage to defend what they know to be right.

I have been trying to get this published as an op-ed, but I am going to post it here since I think it is timely in light of the "consent" extortion events.

Deafening Quiet from the Scientific Establishment

jeremymberg.github.io/jeremyberg.g...

1/14

I would bust out a slide rule for that one

🧪 And House appropriators say: no cuts to NIH budget!

House subcommittee version just came out (link below). Holds NIH flat at $48 billion.

To be clear: this is far from over. But a good sign that science still matters across both sides of aisle.

YOUR VOICE MATTERS!!

I thought this was super cool too! Amazing that they can infer allele specific effects in these kind of data. But in the end I'm not sure it uncovers a ton more parent of origin effects than were previously known?

I always enjoyed visiting DC for neuroscience conferences, but now that they've sent in the storm troopers I'm sure the criminal violations of statistical best practices will finally end

Wow

Can universities go on strike by withholding licensing of all their patents by any US govt agency (incl military)? Seems like the only leverage they have and better than just giving their lunch money to the bullies

Nature retracts paper on novel brain cell type A 2022 paper was retracted after an independent team of researchers reanalyzed the data and questioned its validity.

Interesting to see Nature retracting a study based on apparent over-clustering of single cell sequencing data

www.thetransmitter.org/cell-types/n...

Memory study sparks debate over statistical methods The study used data filtering and statistical approaches that can yield spurious findings, but more rigorous methods can result in missed leads.

A reanalysis of data published in a 2024 Nature paper highlights a “thorny problem” in genetics research: how to balance curiosity and caution when searching for gene candidates.

By Katie Moisse

#neuroskyence

www.thetransmitter.org/statistics/m...

Cool work, Marcelo et al!

Thanks for this thoughtful and lucid exposition of an important issue that (alas) goes well beyond a single paper or group of authors. Neurogenomics deserves rigorous standards, so we don't squander the potential of large-scale sequencing for answering fundamental questions about the brain.

Reply to: Reply to: False positives in the study of memory-related gene expression In the Nature paper “Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory” published on March 14th, 2024, authors Sun et al. claimed to identify cell-type specifi…

I wrote a review of a recent paper on false discovery and multiple testing correction. liorpachter.wordpress.com/2025/06/16/r...

Here's to Good Friends Here's to Good Friends

I guess it really was a Stanford thing...

Ofc the guy bringing EANABS to the party is not going to be the most popular one there, but I guess someone has to help the field avoid a hangover

I remember when I was in grad school the Stanford ugrads were partying too much, so the Univ mandated all gatherings had to have EANABS-- equally attractive non alcoholic beverages.

We need EANABS for stats--methods that are powerful and insightful but without cutting corners in rigor.

Great to see attention being paid to rigor in neuroscience methods.