Happy to share our new preprint on non-coding genetic variation in the human brain and Parkinson's disease. Great team effort with @alexanrna.bsky.social, @juliedeman.bsky.social, Koen Theunis, and all co-authors, supervised by @steinaerts.bsky.social and @jdemeul.bsky.social.
Thread below:
ouch
New paper alert: Our latest shows how maternal diet impacts ribosome levels and early growth intergenerationally in #Celegans
Led by Sigma Pradhan and in collab with @nstroustrup.bsky.social
journals.plos.org/plosbiology/...
@plosbiology.org @izb-unibern.bsky.social @unibe.ch
📣 New preprint 🧵: we profiled post-mortem human BA22 (speech cortex) in autism across 100 donors using single-nucleus multiomics (~500,000 nuclei), integrating RNA + chromatin accessibility. Shout-out to my co-first authors Varun Suresh and Yuhan Hao: www.biorxiv.org/content/10.6...
Our latest publication is now out at Genome Biology!
link.springer.com/article/10.1...
We uncover a unique association between a H3K27me3 reader complex and active transcription.
A thread with our key findings: (1/8)
#TEsky #Polycomb #transcription #smallRNAs
For decades, molecular biology and human genetics have been built around measurements of average gene expression. That was partly conceptual, but also technological: for a long time, the mean was the quantity we could measure most reliably. Our new preprint argues that this framework is incomplete.
Preprint now available.
www.biorxiv.org/content/10.6...
Many biological outcomes may depend not only on shifts in the mean, but on changes in the fraction of cells that cross functional thresholds. That has implications for development, variable penetrance, context-specific cellular responses, and disease-associated effects.
Mean expression tells us how much RNA is produced on average. Gene expression fidelity tells us how precisely that level is achieved across cells. Once that distinction is made, a large set of biological questions comes into view, including questions that mean-based analyses may not capture well.
We found that differences in regulatory fidelity between species often trace to cis-acting variation. This means that fidelity can be studied as a genetically tractable and evolutionarily important dimension of gene regulation.
A central point of the paper is that gene expression fidelity is not just noise. It is a biologically structured trait, a genetically encoded trait, and a trait shaped by natural selection.
We show that mean expression is not the only biologically relevant dimension of gene regulation. A second dimension is mean-corrected cell-to-cell dispersion: how tightly expression is controlled around a target level across cells. We argue that this reflects the fidelity of gene regulation.
For decades, molecular biology and human genetics have been built around measurements of average gene expression. That was partly conceptual, but also technological: for a long time, the mean was the quantity we could measure most reliably. Our new preprint argues that this framework is incomplete.
Beyond the mean: genetic control of gene expression fidelity and dispersion
www.biorxiv.org/content/10.6...
@nygenome.org is hiring Genomic AI Fellows! (fancy postdoc positions) If you're interested in working at the interface of AI and genomics in a great environment please apply at: jobs.silkroad.com/NYGenome/Car...
"Beyond the baseline: mapping the context-specific regulatory landscape of disease"
by Yoav Gilad and Alexis Battle
authors.elsevier.com/sd/article/S...
New review on context-specificity and disease genetics from @ygilad.bsky.social and me:
authors.elsevier.com/sd/article/S...
UAB is recruiting neuroscience faculty at two different levels - come join our vibrant neuroscience community!
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
Pre-print on cardiomyocyte response to novel anti-cancer drug CX-5461 now published! Includes new gene expression response data at higher CX doses. Response to micromolar CX doses starts to mimic DOX responses, suggesting that off-target effects on the heart should be considered for this drug.
I guess it's just hard to focus. I get that.
Anything really, but what I miss most are the paper/preprint announcements and related discussions.
I can hardly find science posts here. I don't know how to change that. Yes, I know a lot is going on (obviously), but I get all the other things everywhere... this was where I used to get the science 😞
Recommended
My daughter Maya, who had to wear a scoliosis brace for 2 years, wants to connect with other teens who live with invisible diseases. www.under-the-iceberg.com/about
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What a joke
Atari?
We're hiring for multiple open rank positions in the broad areas of biochemistry, molecular biology, and computational biology. With the recruitment of a new chair our Departmental strengths now include nuclear architecture, genomics and ancient DNA.
jobs.sciencecareers.org/job/676677/b...
Faculty position at the department of medicine, University of Chicago. Please share.
