🧬 How do immune disease-relevant variants affect gene regulatory networks in CD4+ T cells?
🧪🖥️ We coupled two large-scale CRISPRi screens (>4M cells) to map the downstream cascades of thousands of SNPs
More details in the thread below 👇 or in the article 📖 on biorxiv tinyurl.com/CD4screens
Annique Claringbould
🤝 This was a truly collaborative effort bringing together experimental & computational expertise. Many thanks to the team - esp. my co-lead @dewimoonen.bsky.social; @danielschraivogel.bsky.social and Lars Steinmetz for excellent supervision; and @argschwind.bsky.social, Stefan Schrod +many others!
I’m excited to announce that as of today we are officially releasing “QED for Grants” for everyone. What started off as an extension of our existing paper review platform, grew in the last few months to an entirely new design (2/16)
Out now on bioRxiv! 🧬🖥️
Dewi Moonen, @anniquec.bsky.social and a team led by Lars Steinmetz and Daniel Schraivogel at EMBL have mapped the downstream regulatory networks of thousands of immune disease-relevant variants in CD4+ T cells
www.biorxiv.org/content/10.6...
🧪 We performed genome-wide Perturb-seq on >7500 genes; 12% modulated expression of >10 genes
Variant ➡️ CRE ➡️ gene ➡️ network: we constructed regulatory cascades from disease-associated variants by integrating both screens, which connected 85 enhancer-like elements to 56% of all genes in two steps
🎯 The results help resolve individual immune-related loci (TYK2, DEXI/CLEC16A) and combined disease-relevant biological processes
🦠 We observe shared core immune programs (response to virus, T cell activation), but also disease-specific enrichments (tight junction organisation in celiac disease)
🔢 We overlapped 4,724 genetic variants across 14 immune diseases with cis-regulatory elements that were accessible in CD4+ T cells
⚡️ Perturbing these elements with TAP-seq (tinyurl.com/TAPseq) revealed the genes they regulate. Best computational predictors? ENCODE-rE2G and eQTLs
Did you read our paper applying SUM-seq in macrophages, T-cells and iPSCs (www.nature.com/articles/s41...) and think: I want to try this cost-effective single cell RNA & ATAC-seq method myself? 🧬
Find the complete protocol including tips, troubleshooting and timing now in Nature Protocols
Genome-scale mapping of variant, enhancer and gene function in primary human CD4+ T cells https://www.biorxiv.org/content/10.64898/2026.03.09.710372v1
Here's a little widget to play with the data across journals (as well as download the raw CSVs).
sashagusev.github.io/Genetics_Pub...
