Will Macnair

I made a bot that posts pre-prints of single cell papers: @prepub-singlecell.bsky.social (I posted about it a little while ago when no one was here, so posting again now :D) It's pretty dumb so very open to suggestions for improvements!

I block people who are annoying to people in replies I don't even follow. Your posts suck? Banished forever.

Polars 2.1 is released! Three weeks after 2.0 we're shipping a big one. A few highlights: - Spill to disk for group-by and window functions - Recursive CTE's in SQL - Reading and writing encrypted Parquet - Better memory tracking for out-of-core - And over 90 performance improvements merged 🧵

A reminder, because it is almost that time of year: More children are killed by cars on Halloween than any other day of the year, by far. www.vox.com/future-perfe... If you're a parent, I hope you'll do what you can to keep kids safe. If you're driving on Saturday, PLEASE exercise extra caution.

Single-cell multi-omics reveals archetypal regulatory programs shared across T cell subsets @cp-cellreports.bsky.social www.cell.com/cell-reports... @yuripritykin.bsky.social @princeton.edu

If you've noticed a distinct dialect emerging in frontier AI models and struggled to understand what they're talking about, you're not crazy! We turned to psycholinguistics to investigate what makes the writing style so weird, and why this might be happening 🚨New preprint! 🧵

the story goes like this

Vulnerability xkcd.com/3314/

Systematic review relevant to the discourse on diagnoses and meds. "ADHD was associated with increased all-cause mortality, suicide mortality, unintentional or intentional injury mortality, and natural-cause mortality, whereas ADHD medication use was associated with reduced all-cause mortality."

Equally happy and terrified to share my first preprint of my PhD! Turns out the order of your scRNA-seq QC pipeline matters more than we thought: removing ambient RNA before doublet detection can reduce doublet detection performance!

Turns out the order of your scRNA-seq QC pipeline matters more than we thought: removing ambient RNA before doublet detection can reduce doublet detection performance! Our new paper from the amazing PhD student @michellemeier.bsky.social

Delighted to share this new article where we propose our view for the next generation of human genetics. We argue a need for "Trait Causal Models" linking genetics to effects at all levels of biological structures, and talk about how to get there using gwas, perturbations and observational omics

The consequences of #oligodendrocyte involvement in #Alzheimer’s disease are poorly understood. This Perspective by Charles ffrench-Constant suggests that activity-dependent adaptive myelination by these cells could be perturbed, leading to cognitive loss. 🧪 #AcademicSky plos.io/47iYNMq

If you’re working with Flex data, be careful when doing ambient RNA correction! It turns out that removing ambient RNA (in particular with decontX), and *then* doing doublet ID, can seriously reduce doublet detection performance ‼️

Order Matters: Ambient RNA correction confounds doublet detection in single-cell RNA sequencing #SingleCell 🧪🧬🖥️ https://www.biorxiv.org/content/10.64898/2026.10.13.758369v1

No joke. I think this is the most important video I have ever seen about mobile games. This guy breaks down how this game psychologically profiles you, and makes the game harder or easier in order to show you ads

This is unexpectedly awesome: Zenodo allows reserving a DOI before depositing the materials, so you can include the DOI in the materials themselves. This is very helpful because you can include the identifier in the metadata itself.

I'm dying laughing at how the cat has conformed to her flower shaped bed today

I highly appreciate this directed graph showing which language is used to indicate incomprehensibility in different languages (eg, “it’s Greek to me”)

If you want to see a really good example of the big data paradox in action: www.nature.com/articles/s41...

Beautiful example of how data quality / study design is *absolutely critical*. Big N alone absolutely does not guaranteed good results, and can actually mislead: big N plus bias --> wildly wrong estimates with high confidence 😬

Microglia clear intraneuronal α-synuclein aggregates www.science.org/doi/10.1126/...

This is evidence against the opinion of three different doctors but toward the opinion of two others I've seen. We do not exist in a world where you can "just ask a doctor" for most genuinely hard things.

Update: GOOD NEWS. Really profoundly relieving structural picture. This significantly changes the likelihood we put behind which hypothesis for what's happening to my hands. The imaging I argued for bc of /informed-patient is the only type that could've given us this evidence at this point.

Edward Wright baptized #OTD 1561. In 1599 he proposes the median as a measure of central tendency & methods of variance estimation for navigational application. He is also the first (& so far only) Fellow of Caius College Cambridge to be granted sabbatical leave to be a pirate.

Human microglia clear intraneuronal α-synuclein aggregates by GPNMB-mediated trogocytosis #NeuroDegeneration 🧪🧠 https://www.science.org/doi/abs/10.1126/scitranslmed.adz9258?af=R

So a few folks asking why OAI is releasing this at all. And I think that's probably worth a thread in its own right

We just released Polars 2.0. It removed many of our legacy decisions makes the streaming engine our default and promotes SQL to a first class citizen within Polars. pola.rs/posts/releas...

Fun blog, and it made me long for more connections between philosophy and applied statistics

The share of children who died before they were 5 years old in 1950 and 75 years later. Africa: 33% ↘ 6% Asia: 25% ↘ 2.5% Oceania: 9.3% ↘ 2% Latin America: 21% ↘ 1.5% Northern America: 3.8% ↘ 0.6% Europe: 10.5% ↘ 0.4% Globally: 23% ↘ 3.5%

1/12 Personality predicts earnings and wealth. But does it cause them? That is hard to answer: personality is correlated with family background and much else. In our new working paper, we use the randomness of genetic inheritance to get closer to a causal answer.

Happy birthday Steve Reich appy birthday Steve Reich H ppy birthday Steve Reich Ha py birthday Steve Reich Hap y birthday Steve Reich Happ birthday Steve Reich Happy birthday Steve Reich Happy irthday Steve Reich Happy b rthday Steve Reich Happy bi thday Steve Reich Happy bir

Fantastic preprint showing how circulating EBV-specific CD8+ T cells in MS adopt a GZMK+ effector–memory state that is primed to migrate to the CNS & may drive neuroinflammation through non-cytolytic interactions with B cells & myeloid cells. 🧵👇 1/

New preprint from our lab, now on bioRxiv! We are VERY excited about this one! www.biorxiv.org/content/10.6... How does Epstein–Barr virus (EBV) immunity become linked to multiple sclerosis (MS)? (1/8)

what i think is currently up in the AI space since we're having cost arguments again: selling inference is very profitable, but models are improving so fast that there's no time for capex on model training to amortize, so net at this rate they're losing money which is why they want a cartel

Our single-nucleus immune multiome atlas is now out in @nature.com! 🧬 10M PBMCs from 1,108 @finngen.bsky.social donors recruited by Finnish Blood Service, profiled at @broadinstitute.org with chromatin accessibility and gene expression in the same nuclei, to trace how disease variants act 🧵👇

Made a Printer Friend which quickly transcribes speech onto little slips of paper. Very nice for card sorts, quickly capturing open loops, discursive notes in books, etc. The speed of thermal printers and their auto-cutters is so satisfying! And dedicated mechanical key! Mm!

Imagine if instead of regulating drone risks the normal way (which we did), we instead paid weird bloggers lots of money to worry about superintelligent dogs sprouting thumbs and using drones to kill us. This is pretty much how the US is approaching AI risks and regulations. My latest:

If you are a US citizen or permanent resident looking for a postdoc, the President's Postdoctoral Fellowship Program is a great opportunity faculty.umd.edu/presidentspo...! If you are eligible, working in computational genomics, and interested in my lab, let me know!

Targeted single-nucleus sequencing of 39,800 neurons reveals extensive low-frequency somatic variants #SingleCell 🧪🧬🖥️ https://www.biorxiv.org/content/10.64898/2026.09.21.753260v1

Some random thoughts: Good science doesn't always need disruptors. Often, it needs load-bearing walls. You can't pivot away from a failed multi-year experiment or "iterate" your way out of a mentee's PhD. Science needs stable foundations, not churn. Don't break the people building on top of it.

What AI scales about science are the parts that are most broken and gameable. With the exception of combinatorial problems like protein folding, we need more thinking and less rote computation.

A new publicly available single-cell atlas of the human prefrontal cortex was made from 6.3 million nuclei across 1,494 donors, ranging from before birth to more than 100 years. By @siddhantpusdekar.bsky.social www.thetransmitter.org/transcriptom...

Microglia don't just prune synapses; they also reach into axons and scoop out organelles containing cellular debris, a new preprint reports, calling it "skoupocytosis." #neuroskyence By @siddhantpusdekar.bsky.social www.thetransmitter.org/microglia/mi...

Landmark map of human brain’s gene activity holds clues to Alzheimer’s disease and more #NeuroDegeneration 🧪🧠 https://www.nature.com/articles/d41586-026-02947-x

Single-cell atlas of transcriptomic vulnerability across brain disorders #NeuroDegeneration 🧪🧠 https://www.nature.com/articles/s41586-025-09573-z

Single-nucleus atlas of cell-type specific genetic regulation in the human brain #NeuroDegeneration 🧪🧠 https://www.nature.com/articles/s41588-026-02733-5

🧪Today, the PsychAD Consortium published EIGHT papers across Nature journals detailing their efforts to create the largest map of the human prefrontal cortex. It's hard to overstate the amount of work here, nor the absolute treasure trove this team has created for researchers.

Review @cellcellpress.bsky.social Oligodendrocytes in central nervous system health and disease www.cell.com/cell/fulltex...

It's here! new preprint: Gravlax, an annotation-independent molecular evidence archive for scRNA-seq. A count matrix freezes one annotation. Molecules never change. Instead, gravlax keeps the evidence. Requantify, query, and discover under any annotation. 🧵 www.biorxiv.org/content/10.6...