New preprint from another part of my PhD! ππ
Some mutations arise after fertilisation π§¬, so early they can appear in both a parentβs body and their germ cells.
By analysing family trio genomes πͺ, we built one of the largest catalogues of these βhiddenβ inherited variants yet.
tinyurl.com/mvns2ytv
The final pre-print of the IBDverse project is out now ⨠- looking at the genetics of IBD 𧬠Led by the amazing @tobioinformatics.bsky.social and @bradleyomics.bsky.social
π Huge thanks to our patients, collaborators, and funders @crohnscolitisfdn.bsky.social β this work wouldnβt be possible without you.
Special thanks to my PhD supervisors @carlanderson.bsky.social and Tim Raine for their incredible support and guidance.
𧡠10/10
TL;DR:
π We provide a single-cell resource of mucosal and blood immune cells in Crohnβs disease
π₯ Reveal the unique role of circulating ex-Trms
π Show that inflammation is largely gut-restricted
π§ Open up new paths for biomarker & therapeutic discovery
𧡠9/10
π§ͺ We also saw gut-specific transcriptional remodeling in Naive B cells and Tregs with upregulation of IFN-Ξ³, chemokine, and T cell migration pathways.
Again, none of these were present in the blood π₯²
𧡠8/10
π¬ In terms of cell type abundance, circulating classical monocytes were negatively associated with inflammation, while all the other inflammation-related changes were gut-restricted.
𧬠Reinforcing the tissue-restricted nature of Crohn's inflammation.
𧡠7/10
π§ CD4βΊ ex-Trms were enriched for IFN-Ξ³ signaling, while the pro-inflammatory CD4βΊ subset was enriched for TNFR2 and interleukin signaling.
Many of these inflammation-associated genes were also found in intestinal Tregs and macrophages β two key IBD players.
𧡠6/10
π More importantly ex-Trms were the only blood population whose gene expression correlated with gut inflammation, as measured by the TI-SES-CD scores.
πThese signatures were also shared with their intestinal counterparts.
𧡠5/10
π These ex-Trms were also present in public PBMC scRNA-seq datasets - across IBD, healthy donors, and other inflammatory conditions.
𧡠4/10
π₯ We discovered a rare subset of circulating T cells with Trm-like features (aka ex-Trms).
This included CD8βΊ, CD4βΊ, and a pro-inflammatory CD4βΊ subset expressing KLRB1 and CCR5, previously seen in the gut.
𧡠3/10
𧬠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.
𧡠2/10
π¨ SUPER EXCITED to share our new preprint on the mucosal and circulatory immune landscape of Crohnβs disease!
π©Έ Blood is commonly used in biomarker discovery and drug development, but how well does it reflect what's actually happening in the gut? π
𧡠1/10
π 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 ππ»
Jason Lyon illustration
New paper alert π’! (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... π§΅1/8
"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 π©π»βπ»
Hi everyone!
Here's a starter pack of genomics scientists trained in Mexico π²π½ 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