Anna Cuomo

Impact of Rare and Common Genetic Variation on Cell Type-Specific Gene Expression Understanding the genetic basis of gene expression can shed light on the regulatory mechanisms underlying complex traits and diseases. Single-cell resolved measures of RNA levels and single-cell expre...

For more detail check out the preprint at medrxiv.org/content/10.1..., or get in touch! (12/12)

As always, teamwork makes the dream work, huge thanks to everyone involved: supervisors Joseph Powell and @dgmacarthur.bsky.social, ‪@htanudisastro.bsky.social‬, Ellie Spenceley, @blakebowen.bsky.social, @alberthenry.bsky.social, Hao Lawrence Huang, @anglixue.bsky.social and many others! 👏(11/n)

Other work covering different aspects of this dataset is coming, so stay tuned! Starting with @htanudisastro.bsky.social on the role of tandem repeats in the regulation of single-cell expression :) read more at bsky.app/profile/htan... (updated version coming soon!)(10/n)

In summary, deeply sequenced scRNA-seq from ~2,000 individuals and >5m cells and matched WGS, combined with a powerful sc-eQTL mapping tool allow us to decipher how genetic variants shape the immune landscape at unprecedented resolution 🚀(9/n)

Impact of Rare and Common Genetic Variation on Cell Type-Specific Gene Expression Understanding the genetic basis of gene expression can shed light on the regulatory mechanisms underlying complex traits and diseases. Single-cell resolved measures of RNA levels and single-cell expre...

Check out the preprint to read more about how we define a framework to quantify cell type specificity, identify eQTLs that vary dynamically along biologically-informed cell states, and map cell state abundance QTLs! ‼️ medrxiv.org/content/10.1... (8/n)

For example, we found distinct eQTLs OSM in different cell types, with the NK cells-specific effect (only 👀) colocalizing with a risk locus for IBD (7/n)

We found over 30,000 colocalization events between our eQTLs and GWAS loci from 14 disease phenotypes and 44 blood traits, displaying remarkable cell type specificity (43% disease loci colocalize with an eQTL in only one cell type!) 🤩 (6/n)

These samples were sequenced deeply, with ~3,000 cells per individual across 28 cell types, giving us power to find common eQTLs for 83% of genes and rare variant signal for 47%, with variants often beautifully overlapping with functional annotation + in-house scATAC-seq 😍(5/n)

We leverage WGS to call common *and rare* variants, and use SAIGE-QTL to model single-cell counts, to identify >150,000 common eQTLs and >30,000 rare variant gene-level effects (via Burden + SKAT tests) (4/n)

Efficient and accurate mixed model association tool for single-cell eQTL analysis Understanding the genetic basis of gene expression can help us understand the molecular underpinnings of human traits and disease. Expression quantitative trait locus (eQTL) mapping can help in studyi...

Yet, most single-cell eQTL maps only test for the effect of common variants and use “pseudo-bulk” individual-level aggregated expression, rather than modelling single-cell profiles directly. Both are addressed by our recently introduced, SAIGE-QTL www.medrxiv.org/content/10.1... (3/n)

Single-cell genomics meets human genetics - Nature Reviews Genetics In this Review, the authors describe the emerging field of single-cell genetics, which lies at the intersection of single-cell genomics and human genetics. They review the first single-cell expression...

Population-scale single-cell studies, where matched scRNA-seq and genotype data are available for hundreds (now thousands!) of individuals can transform our understanding of the cell contexts underpinning key processes in human biology and disease www.nature.com/articles/s41... (2/n)

📢 new preprint alert: So so excited to share our analysis on the impact of common and rare variants on single-cell gene expression in blood, using WGS and scRNA-seq data from nearly 2,000 individuals and 5.4m cells as part of TenK10K phase 1 🧬 www.medrxiv.org/content/10.1...
🧵👇 (1/n)

Bluesky now has over 20M people!! 🎉

We've been adding over a million users per day for the last few days. To celebrate, here are 20 fun facts about Bluesky:

This work was driven by brilliant PhD student @htanudisastro.bsky.social as a close collaboration with Joseph Powell’s team, especially postdoc @annasecuomo.bsky.social. Both Anna and Hope will be presenting at #ASHG2024 on Wednesday - we’d welcome comments as we prep the final dataset of over 2K!

give us a couple more weeks!

Sad to be missing #ASHG23, but check out the talk by the brilliant Wei Zhou talk on Saturday on our new scalable & efficient method for single-cell eQTL mapping!

I'm delighted to release the first half of my new textbook in human genetics:
web.stanford.edu/group/pritch...

"An Owner's Guide to the Human Genome: an introduction to human population genetics, variation and disease"

BlueSky for Scientists BlueSky for Scientists Authors: Steve Haroz and Mark RubinURL: http://blueskyscience.steveharoz.com Features you may miss from Twitter or Mastodon As BlueSky is in beta, some features are not impleme...

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