John Mariani

VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization www.nature.com/articles/s4...

The pitfalls of class prediction in omics 🧵
1/ You think you’ve built the perfect omics predictor.
The accuracy is high. The p-value is low.
But is it real—or just a story your data whispered back?

Oligodendrocyte progenitor cell responses to inflammatory demyelination with aging https://www.biorxiv.org/content/10.1101/2025.09.22.677854v1

A host organelle integrates stolen chloroplasts for animal photosynthesis Sea slugs steal foreign chloroplasts and store them in specialized organelles that facilitate photosynthesis and eventual digestion to mediate starvation resistance.

www.cell.com/cell/abstrac...

A host organelle (in sea slugs) integrates stolen chloroplasts for animal photosynthesis

tgv 0.1.0 release: github.com/zeqianli/tgv
- Rich CIGAR and base visualization
- Allele frequency visualization
- VCF and BED file support
- Mouse dragging and hovering
- Filter alignment

Now 90% of what I need from IGV can be done in the terminal.

Some interesting behind-the-scenes:

Single-cell transcriptomic and genomic changes in the ageing human brain - Nature Sequencing analyses of human prefrontal cortex from donors ranging in age from 0.4 to 104 years show that ageing correlates with an accumulation of somatic mutations in short housekeeping genes and a reduction in the expression of these genes.

Nature research paper: Single-cell transcriptomic and genomic changes in the ageing human brain

go.nature.com/4mRVCl0

H3K79 methylation and H3K36 trimethylation synergistically regulate gene expression in pluripotent stem cells H3K79me and H3K36me3 synergistically dampen gene expression to facilitate cellular differentiation.

H3K79 methylation and H3K36 trimethylation synergistically regulate gene expression in pluripotent stem cells

www.science.org/doi/10.1126/...

Check it out, Chromatin Kids!

Chromatin remodeller does stuff to Transcription Factors!

Functions where it is seldom seen!

Both decreases and increases chromatin accessibility!

How cool is that?

EBV induces CNS homing of B cells attracting inflammatory T cells - Nature Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.

How does Epstein- Barr virus induce multiple sclerosis?
The infection leads to B cells that get into the brain, attracting pro-inflammatory T cells (mouse model)
www.nature.com/articles/s41...

Coming back to a 2 year old script...

Many proteins bind RNA, yet we still don’t know what RNAs most bind because methods map one RBP at a time. In @cp-cell.bsky.social, with the Jovanovic lab, we describe SPIDR – a method for mapping the RNA binding sites of dozens of RBPs in a single experiment. www.sciencedirect.com/science/arti...

I've been to two bars tonight and both had feels so good playing

Pan-viral ORFs discovery using massively parallel ribosome profiling Defining viral proteomes is crucial to understanding viral life cycles and immune recognition but the landscape of translated regions remains unknown for most viruses. We have developed massively para...

With the help of a technique called Massively Parallel Ribosome Profiling, researchers in Science have identified more than 4000 open reading frames—stretches of genetic material that can encode proteins—across 679 human-associated viral genomes. scim.ag/43RoAdF

Myelin–axon interface vulnerability in Alzheimer’s disease revealed by subcellular proteomics and imaging of human and mouse brain
www.nature.com/articles/s41...

Protective exercise responses in the dentate gyrus of Alzheimer’s disease mouse model revealed with single-nucleus RNA-sequencing - Nature Neuroscience Dissecting the adaptive exercise response of the neurogenic stem-cell niche in the dentate gyrus by single-nucleus RNA sequencing reveals the molecular mediators that underlie exercise’s protective ef...

How exercise protects the brain through neurovascular-associated astrocytes and neuroplasticity:
Results of elegant single cell/nuceli studies in the experimental Alzheimer's model
www.nature.com/articles/s41...

Posit Accelerate model deployment with Databricks and Orbital for R and Python Scikit-learn/Tidymodels projects.

Being able to productionize a ML model is often the goal, however there are many things to keep track of when you do. The orbital package lets you translate your fitted scikit-learn or tidymodels model into SQL that that when run produces predictions.

posit.co/blog/databri... #python #rstats

Posit We’re happy to announce that we’re supporting Typst by funding one of their full-time engineers.

At Posit, we love @typst.app:

⚡ Make PDFs in milliseconds, not minutes
✨ The power of LaTeX with today's technologies
✍️ Modern typography (including emojis!)
🧠 Clear mental model

So I'm thrilled to announce that we're now supporting its development: posit.co/blog/posit-a...

#rstats

Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion. https://www.biorxiv.org/content/10.1101/2025.05.27.654663v1

This is why science funding matters.

We uncovered a hidden signaling system in the brain—one that responds to maternal environment, even to drugs like LSD during pregnancy.

It took 5 years, a brilliant team, and public funding to get here.

Out today in @NatureNeuro: 🧵👇

Surprising they didn't use Grok

This is a solid title

I was having a hard time describing how a plate of cultured cells didn’t look healthy to a new undergrad in the lab. He looked at them and said, “oh yeah, the vibes are off.” Thank god for Gen Z.

Activity-driven myelin sheath growth is mediated by mGluR5 - Nature Neuroscience Employing pharmacology, genetics and all-optical approaches in zebrafish, Braaker et al. find that neuronal activity influences the growth of myelin sheaths along axons by signaling through metabotrop...

For those who want a distraction and/ or are interested, here's the latest from the group, led by Phil Braaker

www.nature.com/articles/s41...

ATAC-seq quality is highly dependent on Tn5 activity, a function of your enzyme AND your sample. It is strongly recommended to perform Tn5 titration experiments to determine the appropriate amount of enzyme. Too much, and you lose chromatin information. Too little, and you lose complexity 1/

Childhood adversity as a risk factor for autoimmune disease: A systematic review and meta-analysis with implications for psychiatry Autoimmune diseases are a heterogeneous category of disorders caused by an interaction between genetic and environmental factors which lead to a dysre…

Childhood adversity as a risk factor for autoimmune disease: A systematic review and meta-analysis with implications for psychiatry www.sciencedirect.com/science/arti...

SORRY, NERDS 5/4 1s DAVE BRUBECK DAY

#MusicSky #MayTheFourth

Charting the transition from in vitro gliogenesis to the in vivo maturation of transplanted human glial progenitor cells Neither rodent models nor in vitro studies of human cells adequately describe the molecular ontogeny of human glial progenitor cells (hGPCs). Here, we used scRNA-seq together with scATAC-Seq and CUT&T...

New preprint exploring how transplanted human glial progenitors mature and differentiate in vivo 🧬

www.biorxiv.org/content/10.1...

So beautiful!! Amazing work! Congratulations to all authors 🤩

I found the most incredible graph on the other site