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Tobi Alegbe

@tobioinformatics.bsky.social
127 followers 173 following 31 posts

I look at small things on a big scale Single-cell data scientist at Open Targets, EMBL-EBI. Previously StatGen PhD student at Sanger Institute

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Reposted by Tobi Alegbe
Open Targets @opentargets.org · 04/08/2026
6 years 646 patients 1193 samples 100 endoscopists 9 lab scientists 3 postdocs 2 PhD students 502 courier runs from Addenbrooke’s Hospital to @sangerinstitute.bsky.social IBDverse is the largest single-cell dataset of Inflammatory Bowel Disease (IBD)—and generating the data for it was no mean feat
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Open Targets @opentargets.org · 15/06/2026
Out now in Nature Genetics! The largest single-cell RNA sequencing dataset of terminal ileal biopsies profiles 1.1 million cells from over 100 Crohn’s disease patients and over 200 healthy controls. Crohn’s disease is a type of inflammatory bowel disease (IBD) www.nature.com/articles/s41...
nature.com
Single-cell RNA sequencing of terminal ileal biopsies identifies signatures of Crohn’s disease pathogenesis - Nature Genetics
IBDverse is a single-cell RNA atlas of terminal ileal biopsies comprising 1.1 million cells from 111 patients with Crohn’s disease and 232 healthy participants. Analysis of the data identifies genes, ...
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Tobi Alegbe @tobioinformatics.bsky.social · 12/06/2026
Gothenburg airport currently flaunting the longest line of geneticists in the world. @pacbio.bsky.social can you beat this on Sunday? #ESHG2026
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Tobi Alegbe @tobioinformatics.bsky.social · 07/06/2026
Delighted to see this out, check out my pinned post for a run through of the findings from when it was a preprint!
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Tobi Alegbe @tobioinformatics.bsky.social · 07/06/2026
We were very privileged to have you contribute and I was personally very privileged to have you as my secondary supervisor - thanks Chris!!
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Chris Wallace @chr1sw.bsky.social · 07/06/2026
Very privileged to have played a small part in this single cell eqtl study of intestinal and blood cells. Led by the fabulous @carlanderson.bsky.social @tobioinformatics.bsky.social @bradleyomics.bsky.social.
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Open Targets @opentargets.org · 08/12/2025
#OnThisDay 10 years ago, we launched the Open Targets Platform! 🎂 🧬🖥️
Graphic with a 10 surrounded by fireworks and the Open Targets Platform logo
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Matthew Neville @mattneville.bsky.social · 08/10/2025
Now published! Our paper on: (1) Accurate sequencing of sperm at scale (2) Positive selection of spermatogenesis driver mutations across the exome (3) Offspring disease risks from male reproductive aging [1/n] www.nature.com/articles/s41...
nature.com
Sperm sequencing reveals extensive positive selection in the male germline - Nature
A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.
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Kaur Alasoo @kauralasoo.bsky.social · 02/10/2025
Happy to share that this work together with @opentargets.org is now out at Nature Communications.
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Tobi Alegbe @tobioinformatics.bsky.social · 12/09/2025
Shamelessly adapted from this www.reddit.com/r/Programmer... with nano banana
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Tobi Alegbe @tobioinformatics.bsky.social · 12/09/2025
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Wellcome Sanger Institute @sangerinstitute.bsky.social · 27/08/2025
Scientists have uncovered hidden genetic drivers of conditions like IBD by stimulating immune cells. 🔬 The findings have resulted in a dataset called MacroMap, which offers insight into why some people are vulnerable to certain conditions. sanger.ac.uk/news_item/ac...
sanger.ac.uk
Activated immune cells reveal hidden drivers of autoimmune diseases
A new resource, MacroMap, provides a rich dataset that researchers can use to explore genetic mechanisms behind complex diseases.
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Tobi Alegbe @tobioinformatics.bsky.social · 27/07/2025
KELLYGOAT
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Tobi Alegbe @tobioinformatics.bsky.social · 09/07/2025
expect going in! More in prev paper if you're curious: medrxiv.org/content/10.1101/2023.09.06.23295056v3.full-text
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Tobi Alegbe @tobioinformatics.bsky.social · 09/07/2025
a bit older than the disease arm (as you typically get screened for things later in life) and potentially had a family history of bowel cancer. The uninflamed CDs (but had history of inflammation in biopsied region) were very similar to the healthies, transcriptomically at least, which I didn't
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Tobi Alegbe @tobioinformatics.bsky.social · 09/07/2025
Thanks! And fairly healthy! The controls were getting an endoscopy for innocuous reasons (e.g. anaemia surveillance or bowel cancer screens) but excluded if they had a history of cancer, were on antibiotics or any immune modulating medication. The unhealthiest things about them were that they skewed
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
Guilty of this trope and agree with the point!
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
It seems like it may act via c-Rel/ERK which leads to expression of IL12/IL23. In all honesty we've had a fair few cool findings (and some fires to put out!) so I haven't had the time to flesh this out as much as it deserves - hoping we can whilst under review! www.sciencedirect.com/science/arti...
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
Thanks Luke! Hopefully MAML2 is a familiar sight as it's a locus from Jostins, Ripke et al. 2012 and although our cis-eQTL is a novel coloc, it has colocalised with trans pQTLs for IL12A and IL12B (targeted by ustekinumab afaik). Really cool locus + coloc! platform.opentargets.org/credible-set...
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…samples or assisting with analysis. Also the folk outside those groups who contributed! Thank you!! A huge thanks to our funders @opentargets.org, @crohnscolitisfdn.bsky.social & @wellcometrust.bsky.social trust. And finally thank you to the individuals who donated samples to make this all possible
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
I’ve loved working on this project (IBDverse) and these results wouldn’t have been possible without co-first author @bradleyomics.bsky.social the two supervisors @carlanderson.bsky.social and Tim Raine, as well as everyone in their teams, especially those who played a direct role processing…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
Sadly this thread is long enough without me diving into genetics too but fortunately co-first author and eQTL superstar @bradleyomics.bsky.social has made an excellent thread covering our thoughts as to WHY we think sc-eQTL approaches are better-suited to GWAS: bsky.app/profile/brad...
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
Whilst we’re incredibly excited about our biological findings, what excites us most is that this tissue-based, single-cell approach could be applied to other complex diseases to gain similar insights and unlock the hidden potential of GWAS!
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…past phase 3 clinical trials in-part due to the gastrointestinal symptoms that even included IBD in one individual! Our results could’ve identified these symptoms arising without the expensive clinical trials - human genetics can identify novel targets AND safety issues!
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…are both existing targets for gamma secretase inhibitors (Alzheimer’s) and mitochondrial complex I inhibitors/metformin (diabetes), respectively. But both drugs have had IBD-like side effects reported (diarrhoea, weight loss, abdominal discomfort/bleeding). GSIs never made it…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
Last but by no means least, we chose to take a reversed approach and check which of our colocalised IBD genes were ALREADY drug targets for non-IBD diseases. With a little help from @chembl.bsky.social and @opentargets.org , we noticed two particularly interesting cases: PSEN2 and NDUFAF1…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…in and/or explained the most variance in epithelial cell types, offering a possible avenue to therapeutics which don’t target the immune system (unlike most IBD drugs). But the role of Wnt signalling in cancer necessitates a careful approach to avoid harmful side effects.
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
Another story which emerged was that many eQTLs for genes involved in Wnt signalling colocalised with independent IBD GWAS loci too! These included MYC (a cancer gene), RNF14 (eQTL only seen in inflamed bowels), FUBP1 (binds MYC) amongst others. These eQTLs were observed…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…by leaning on the diversity of cell types in our atlas AND the genotype data paired with each cell type, we were able to probe where the lead variant’s effect was strongest and identify likely effector cell types for these Notch pathway genes, which were both strongest in cDCs!
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…MAML2 and ZMIZ1 (both key players in Notch signalling) - they each had an eQTL colocalise with an independent IBD GWAS locus, on chromosomes 11 and 10, respectively. And both showed the strongest evidence of colocalisation in very distinct cell types (T cells and macrophages) but…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
..and what we found was STRIKING! With our high resolution, IBD-relevant, single-cell data, our eQTLs colocalised with 74 (!) genomic regions where IBD genes couldn’t previously be found (more in @bradleyomics.bsky.social ’s thread as to why we think this might be). These genes included…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
We used this atlas to map eQTLs (genome-wide association of genetic variants to gene expression) across the 86 cell types and 9 major populations in our atlas. With statistical colocalisation, we tested if our eQTLs were driven by the same genetic variants as IBD GWAS signals…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…as a result generated a HUGE cross-tissue single-cell atlas using the three most relevant tissues for IBD: terminal ileum (most frequently inflamed in Crohn’s), rectum (most frequently inflamed in colitis) and IBD blood (enriched for immune cells often tricky to find in gut).
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
…thus there is a need for new IBD drugs to be developed. As reported by @OpenTargets and others, drug targets with genetic support are far more likely to be approved for use in the clinic. We set out to create a dataset for finding novel IBD genes supported by genetics and…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
Inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis are incurable, often debilitating diseases which affect 1 in 123 people in the UK. Whilst drugs exist to treat them, for many these can be ineffective or lose efficacy over time…
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Tobi Alegbe @tobioinformatics.bsky.social · 08/07/2025
🚨New preprint just dropped 🚨 medrxiv.org/content/10.1101/2025.06.24.25330216 The main output from my PhD is finally public and we’re SUPER excited about the findings! If you’re interested in what we learnt about IBD with a massive 700+ sample sc-eQTL dataset of the gut, read on!
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Tobi Alegbe @tobioinformatics.bsky.social · 05/06/2025
An awesome preprint by a superstar PhD student looking at the utility of blood vs tissue in the context of disease!
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Lucia Ramirez-Navarro @luciaramirez.bsky.social · 04/06/2025
🚨 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...
medrxiv.org
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...
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Gareth-Rhys Jones @gastrogrj.bsky.social · 27/11/2024
Heading to #EMDS24 in 🇦🇹 this week? Come hear about our work on the "inflammatory handbrake" exerted by intestinal monocytes in human IBD and murine colitis through ACOD1. Wednesday, Session 4 1640-55; See you there! www.biorxiv.org/content/10.1...
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