I'm excited to share that our work studying gene dosage response curves (GDRCs) is now out in Cell Genomics (@cellpress.bsky.social). www.cell.com/cell-genomic... [1/n]

Buffering of gene dosage response curves for human complex traits

Milind et al. explore why loss-of-function variants and duplications tend to have average effects in the same direction on 94 complex traits. Using gene dosage response curves (GDRCs), they gather evi...

cell.com

Excited to share this preprint that describes my latest work on using GPUs to accelerate processing of RNA-seq data. The title says it all: "RNA-seq analysis in seconds using GPUs" now on biorxiv www.biorxiv.org/content/10.6... and github github.com/pachterlab/k... Figure 1 shows they key result

If you research or are simply interested in human genetic variation, ancient and modern, read my and Noah Rosenberg's latest in GENETICS academic.oup.com/genetics/art... 1/2

Reflections on the Human Genome Diversity Project: a conversation with Marcus W. Feldman, Henry T. Greely, and Mary-Claire King

Abstract. The Human Genome Diversity Project (HGDP) began in 1991 as an initiative to study genetic variation from human populations worldwide. In 2002, th

academic.oup.com

First, a couple of weeks ago: www.biorxiv.org/content/10.6... Single cell RNAseq on blood from 200 donors across 4 sites in Indonesia spanning regional axes of genetic and environmental diversity. This is one of very few scRNA data sets from the Global South, including urban and rural settings.

Finally, today's offering! www.biorxiv.org/content/10.6... This began life as a very different project which failed because we couldn't agree on defining eqtl sharing across cohorts. So two young members of the lab dug deeply into this - first @ijbeasley.bsky.social, then @patrickgibbs.bsky.social

Over a year ago, along with Gary Churchill at Jackson Labs, we explored the impact of dietary restriction on lifespan in one of the largest studies using 960 female Diversity Outbred mice. Caloric restriction and intermittent fasting both extended lifespan proportionally to the level of restriction.

Ribosomal RNA (rRNA) genes are found in hundreds of copies in the human genome. Do sequence variations in these paralogs change the ribosome function? Yes! I am excited to share our new preprint @mbarnalab @jkpritch in collaboration with Calico: www.medrxiv.org/content/10.1... 1/8

Three years ago, we showed ~70% of lifespan variation in yeast traces to rDNA copy number. Ribosomal DNA, encoded as 5S and 45S subunits in hundreds of copies, vary substantially across humans. Does this copy number variation, and sequence variation within these paralogs, matter for humans?

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

Disease-associated loci share properties with response eQTLs under common environmental exposures

Many of the genetic loci associated with disease are expected to have context-dependent regulatory effects that are underrepresented in the transcriptomes of healthy, steady-state adult tissues. To un...

biorxiv.org

being an indie bookseller in the helltimes has felt both very stable and very stabilizing, and part of me wishes everyone could be on my side of the counter for a little while, because I think it would help some of you be a little less cynical and doomy right now. so here is my VERY anecdotal data:

Bluetorial: Women, courage, and leadership What follows will include some generalizations based on population averages of what I have experienced over the course of my career. There are, of course, exceptions in every group who are substantially more to one extreme or the other.

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I have a brilliant scientist in my group. She proposed we approach our science as a once in a lifetime opportunity. So, let's do the risky experiments, think deeply, write beautifully, and show reverence to the most awe-some career @inikon.bsky.social

Thanks to all of the NIHers and their friends who reached out to me. I am still here (DM me or Signal jeremymberg.78) I still have a very incomplete picture but based on what I have been told, the damage to NIH and to many wonderful people who work(ed) there is/was impossible for me to imagine 1/n

It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.

1. Today the NIH director issued a new directive slashing overhead rates to 15%. I want to provide some context on what that means and why it matters. grants.nih.gov/grants/guide...

Modern-Day Oracles or Bullshit Machines? Jevin West (@jevinwest.bsky.social) and I have spent the last eight months developing the course on large language models (LLMs) that we think every college freshman needs to take. thebullshitmachines.com

INTRODUCTION

thebullshitmachines.com

scATAC-seq generates more accurate and complete regulatory maps than bulk ATAC-seq www.nature.com/articles/s41...

scATAC-seq generates more accurate and complete regulatory maps than bulk ATAC-seq - Scientific Reports

Scientific Reports - scATAC-seq generates more accurate and complete regulatory maps than bulk ATAC-seq

nature.com

The thing about science is that if a phenomenon such as climate science weren’t real, they wouldn’t need an executive order forbidding its study. The better we explain the social processes of science, the clearer it will be to everyone that this EO is an admission that climate change is real.

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 🧵

My book, An Intuitive Primer on Effective Functional Genomics Study Design, is published! I’d really appreciate it if you could help spread the word, and I’d love to hear your thoughts and feedback. I hope people will find it useful. It’s available on Amazon: tinyurl.com/mx2hewen

Time to share our organelle proteome paper out in @cellcellpress.bsky.social: doi.org/nzwz We created a spatial map of human cells using organelle immunoprecipitation at scale. Locate your fav protein among the 7,600 we mapped across 19 subcellular compartments: organelles.sf.czbiohub.org/ 1/3 🧪

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

I'm gathering that Bluesky is less interested in long science threads 🧪, but I need you all to know the majesty that is the pea aphid, Acyrthosiphon pisum: It can 'feed' on sunlight; gives birth to live, pregnant clone-babies; needs to be bacterially infected to survive. Photo by Shipher Wu.

So, you may ask, why do I get so angry about the new liberal spin on RFK Jr, as in, "he gets some things right, so let's collaborate on those" or "we have to work with him because he has a huge following we need to reach"? Because I've seen this movie before. 1/

Why probability probably doesn’t exist (but it is useful to act like it does) www.nature.com/articles/d41... David Spiegelhalter doesn't appear to be on bsky but he wrote this wonderful piece that came out in Nature just before the holidays

Why probability probably doesn’t exist (but it is useful to act like it does)

All of statistics and much of science depends on probability — an astonishing achievement, considering no one’s really sure what it is.

nature.com

my #1 duty to students is to teach them how to think. AI makes this job harder not easier. A closely related duty I owe is to not let students become accomplices in their own future irrelevance just because it’s easier short term to cheat thinking w AI

Mark Copelovitch@mcopelov.bsky.social · 2y ago

No, they're not caught between anything. Stop it. The fact that AI may be used or useful in future jobs does not create a single dilemma at all for college students in how to actually complete their coursework. This is all nonsense & excuses for not doing the reading & learning how to think & write.

Bluetorial: Adventures with tenure-Part 1

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Thrilled to see this paper out!! 🧪 Spatial transcriptomics of brain aging and 'spatial aging clocks' identify cells that have pro-aging or pro-rejuvenating effects on their neighbors! Huge CONGRATS to Eric Sun and all authors! Fantastic collaboration with @jameszou.bsky.social! rdcu.be/d33uQ 🧵

Spatial transcriptomic clocks reveal cell proximity effects in brain ageing

Nature - A spatially resolved single-cell transcriptomics map of the mouse brain at different ages reveals signatures of ageing, rejuvenation and disease, including ageing effects associated with T...

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Specificity, length, and luck: How genes are prioritized by rare and common variant association studies https://www.biorxiv.org/content/10.1101/2024.12.12.628073v1

Today's Bluetorial: Dealing with Deans (Part 1)

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