Mapping the transcriptomic cosmos of inflammatory bowel disease
Single-cell analysis of IBD tissues at a population scale
We generated the largest single-cell datasets of inflammatory bowel disease relevant samples, spanning millions of cells across the ileum, blood and rectum, from hundreds of individuals with and without inflammatory bowel disease. We were able to perform well-powered analyses comparing the effects of disease, location and genetics on cellular expression.
-
Transcriptomic consequences of ileal inflammation
Comprehensive profiling of terminal ileum cell types, highlighting cell types present in the termninal ileum, key differences between inflamed and uninflamed bowels and which cell types are enriched for dysruptive genetic variants.
Krzak, Alegbe, Taylor, Jones et al.
-
Blood and gut immune comparison
Identification and quantification of the differences in immune cells between blood and gut samples from individuals with Crohn's disease. Several populations and processes are seen to be enriched in either tissue and blood.
Ramirez-Navarro et al.
-
sc-eQTLs to unlock GWAS
Identification of eQTLs within single-cell resolved cell types from ileum, rectum and blood. Integrating these eQTLs with exist disease risk GWAS offers insight into the genes and cell types causally driving inflammatory bowel disease.
Alegbe, Harris et al.
-
Future studies
Building on the foundations that this work has laid down we intend to take further steps to use single-cell RNA-sequencing approaches to better understand IBD biology. These include:
For patients, friends and family
Get straightforward answers about our datasets, publications, and findings. Designed for those who have or know someone who has an inflammatory bowel disease such as Crohn's disease or ulcerative colitis.
What do these datasets mean for me?
Our datasets are available for researchers to download and use enabling others to perform research that can help find answers about inflammatory bowel diseases
What did you discover?
We have released three manuscripts detailing our findings for the wider scientific and medical community to read. These manuscripts are not written with the public in mind and can contain highly technical terminology so we have also written a short summary of these findings which can be found here.
Can I access my data?
All patient information is confidential so we cannot identify individuals to return data. The anonymised data is available to download on this page but will likely be difficult to interpret without appropriate bioinformatic training.
We do provide a means for patients to interact with physical representations constructed from visualisations of their data. These
Who paid for this project?
The project was funded by:
- Crohn's and Colitis Foundation, a charity dedicated to supporting people with and funding research into inflammatory bowel diseases
- The Wellcome Trust, a charity which supports many forms of biomedical research primarily in the UK and provides core funding for the Wellcome Sanger Institute
- Open Targets, a collaboration between academia and pharmaceutical partners seeking to develop new treatments for inflammatory bowel diseases
Can I ask a member of the team about this work?
Yes. A contact email address for the authors of these studies is provided at the bottom of this page. Please note that these questions should only be related to this work rather than IBD in general.
How can I get help with my IBD?
We are primarily research scientists and cannot offer medical advice into the treatment of IBD. You should contact your doctor if you have issues with your disease.
Explore the IBDverse
Here we present the IBDverse data from each of our three papers in both an interactive and downloadable format, allowing IBD researchers the opportunity to conduct their own focused analyses.
-
Terminal ileum single-cell analyses in health and disease
Single-cell RNA-sequencing data and results from 111 CD patients and 232 healthy controls
Download results
DGE: CD [inflamed] vs healthy
DGE: CD [uninflamed] vs healthy
DGE: CD [inflammation severity]
DGE: Age
DGE: Sex
DGE: Organoid [stim.] vs organoid [unstim.]
DGE: Organoid [CD unstim.] vs organoid [healthy unstim.]
Heritability partitioningExplore data
CellxGene browser (atlas anndata)
Download data
Atlasing anndata (70 samples)
Analysis anndata (343 samples)
Organoid anndata (14 samples)
Individual metadata (343 individuals)Authors
Research led by Monika Krzak, Tobi Alegbe, Leland Taylor and Gareth-Rhys Jones with contributions from a multidisciplinary team under the direction of senior investigators Carl Anderson and Tim Raine.
-
Paired immune cell profiling between the intestine and blood
Comparison of immune cell populations between blood and terminal ileum from the 125 individuals with Crohn's disease.
Download results
DGE: Blood vs TI [available upon publication]
DGE: Inflammation [available upon publication]Explore data
CellxGene browser (atlas anndata) [available upon publication]
Download data
Atlas anndata [available upon publication]
Analysis anndata [available upon publication]
Individual metadata [available upon publication]Authors
Research led by Lucia Ramirez-Navarro with contributions from a multidisciplinary team under the direction of senior investigators Tim Raine and Carl Anderson.
-
eQTL mapping across IBD-relevant tissues
Joint single-cell eQTL analysis across terminal ileum, rectum, and blood in over 732 samples from 421 individuals.
Download results
TI eQTLs [available upon publication]
Rectal eQTLs [available upon publication]
Blood eQTLs [available upon publication]
Cross-tissue eQTLs [available upon publication]
Interaction eQTLs [available upon publication]
IBD colocalisations [available upon publication]Explore data
CellxGene browser (atlas anndata) [available upon publication]
eQTL visualiser [available upon publication]Download data
Atlas anndata [available upon publication]
Analysis anndata [available upon publication]
Genotype array data [available upon publication]
Individual metadata [available upon publication]Authors
Research led by Tobi Alegbe and Bradley Harris with contributions from a multidisciplinary team under the direction of senior investigators Carl Anderson and Tim Raine.
Core analysis team
Carl Anderson
Co-senior investigator
Tim Raine
Co-senior investigator
Bradley Harris
Postdoctoral fellow
Cristina Cotobal Martin
Senior Staff Scientist
Gareth-Rhys Jones
Clinical fellow
Leland Taylor
Postdoctoral fellow
Lucia Ramirez-Navarro
Predoctoral fellow
Monika Krzak
Postdoctoral fellow
Rebecca McIntyre
Principal Staff Scientist
Tobi Alegbe
Predoctoral fellow
Clinical team
Our clinical team in the department of gastroenterology at Addenbrooke's hospital collected pinch biopsies during routine endoscopic procedures and sent them via courier for sequencing at the Wellcome Sanger Institute.
It consisted of Claire Dawson, Tina Thompson, Kenneth Arestang, Wendy Garri, Biljana Brezina, Charry Queen Caballes, Nilanga Nishad and Miles Parkes.
Laboratory team
Our laboratory team within the Anderson Lab at the Wellcome Sanger Institute developed a novel protocol for the processing of gastrointestinal biopsies in a gentle manner. They applied this protocol to over 600 IBDverse biopsies (together with processing over 100 blood samples) in order to curate the high quality single-cell datasets.
Under the leadership of Rebecca McIntyre and Cristina Cotobal Martin, it consisted of Mennatallah Ghouraba, Michelle Strickland, Noor Wana, May Xueqi Hu, Jason Skelton, Tong Deng, Jasmin Ostermayer and Kimberly Ai Xian Cheam.
Computational team
Once the data was generated, many individuals in the Anderson group at the Wellcome Sanger Institute performed quality control and data analysis to produce the processed datasets and arrive at the conclusions presented in our manuscripts.
It consisted of Monika Krzak, Tobi Alegbe, Leland Taylor, Lucia Ramirez-Navarro, Bradley Harris, Moritz Przybilla, Marcus Tutert, Ciro Ramirez Suastegui, Hanna Najgebauer, Saniya Khoullar and Eleonora Khabirova.
Collaborators
Outside of the above working teams we were fortunate enough to collaborate with many individuals, both internal and external, who were crucial to our research effort. This included Laura Fachal, Velislava Petrova, Carla Jones Bell, Nikolaos Panousis, Matiss Ozols, Guillaume Noell, Steven Leonard, Reem Satti, Daniele Corridoni, Vivek Iyer, David Ochoa and Chris Wallace.
