Lucia Ramirez-Navarro

Landscape of parental postzygotic mutations in >11,000 rare disease trios Postzygotic mutations (PZMs) arising post-fertilisation, prior to primordial germ cell specification, may be subsequently inherited by both somatic and germ cells, causing somatic mosaicism in the par...

New preprint from another part of my PhD! 📝👇

Some mutations arise after fertilisation 🧬, so early they can appear in both a parent’s body and their germ cells.
By analysing family trio genomes 👪, we built one of the largest catalogues of these “hidden” inherited variants yet.

tinyurl.com/mvns2ytv

The final pre-print of the IBDverse project is out now ✨ - looking at the genetics of IBD 🧬 Led by the amazing @tobioinformatics.bsky.social and @bradleyomics.bsky.social

🙏 Huge thanks to our patients, collaborators, and funders @crohnscolitisfdn.bsky.social — this work wouldn’t be possible without you.
Special thanks to my PhD supervisors @carlanderson.bsky.social and Tim Raine for their incredible support and guidance.

🧵 10/10

TL;DR:

📘 We provide a single-cell resource of mucosal and blood immune cells in Crohn’s disease
🔥 Reveal the unique role of circulating ex-Trms
📍 Show that inflammation is largely gut-restricted
🧭 Open up new paths for biomarker & therapeutic discovery

🧵 9/10

🧪 We also saw gut-specific transcriptional remodeling in Naive B cells and Tregs with upregulation of IFN-γ, chemokine, and T cell migration pathways.

Again, none of these were present in the blood 🥲

🧵 8/10

🔬 In terms of cell type abundance, circulating classical monocytes were negatively associated with inflammation, while all the other inflammation-related changes were gut-restricted.

🧬 Reinforcing the tissue-restricted nature of Crohn's inflammation.

🧵 7/10

🧠 CD4⁺ ex-Trms were enriched for IFN-γ signaling, while the pro-inflammatory CD4⁺ subset was enriched for TNFR2 and interleukin signaling.

Many of these inflammation-associated genes were also found in intestinal Tregs and macrophages — two key IBD players.

🧵 6/10

📈 More importantly ex-Trms were the only blood population whose gene expression correlated with gut inflammation, as measured by the TI-SES-CD scores.

👉These signatures were also shared with their intestinal counterparts.

🧵 5/10

👀 These ex-Trms were also present in public PBMC scRNA-seq datasets - across IBD, healthy donors, and other inflammatory conditions.

🧵 4/10

🔥 We discovered a rare subset of circulating T cells with Trm-like features (aka ex-Trms).

This included CD8⁺, CD4⁺, and a pro-inflammatory CD4⁺ subset expressing KLRB1 and CCR5, previously seen in the gut.

🧵 3/10

🧬 We performed single-cell RNA-seq on paired ileum and blood samples from 125 CD patients with matched endoscopy scores (TI-SES-CD), capturing shared and tissue-specific immune states.

🧵 2/10

Tissue-specific and circulatory immune signatures of mucosal inflammation in Crohn's disease Crohn's disease (CD) is a heterogeneous disease characterized by chronic inflammation of the gastrointestinal tract driven by an aberrant immune response. To understand the immune mechanisms underlyin...

🚨 SUPER EXCITED to share our new preprint on the mucosal and circulatory immune landscape of Crohn’s disease!

🩸 Blood is commonly used in biomarker discovery and drug development, but how well does it reflect what's actually happening in the gut? 👀

🧵 1/10
🔗 www.medrxiv.org/content/10.1...

All these measures will not only affect US-based science but worldwide (eg. developing countries).
Guess so much about equity in genomics?
Hopefully, other (maybe non-US) alternatives arise from this 🙏🏻

Jason Lyon illustration

New paper alert 📢! (Cell) @cp-cell.bsky.social
- How does immune responses to solid tumors vary by age and tumor characteristics in children?! www.cell.com/cell/fulltex... 🧵1/8

Women faculty feel ‘pushed’ from academia by poor workplace climate The gender gap in faculty attrition worsens after tenure, according to a new study

"Women full professors are 19% more likely than men at the same career stage to leave academia, as compared with 6% for women assistant professors and 10% for associates."

This is really horrific. These single cell reference atlases are widely used as is to train all kinds of models! This is one of the reasons I've constantly harping about uniform reprocessing & extremely careful QC of large atlases. 1/

Today, I got the opportunity to present at #ISCBLA2024 about how we are using single-cell to identify circulating and tissue specific signatures in Crohn's disease 👩🏻‍💻

Hi everyone!

Here's a starter pack of genomics scientists trained in Mexico 🇲🇽 including from #LCG-UNAM #LCG-EJ-UNAM undergrads, #RMB / #NNB-UNAM / @cdsbmexico.bsky.social workshops, and more

It's in an early stage and I'm trying to get more to join us here at #AcademicSky

go.bsky.app/5bWBN5V