Public-private partnership using human genetics and genomics data for systematic drug target identification and prioritisation. http://blog.opentargets.org
Open Targets
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Congratulations to the team at the @sangerinstitute.bsky.social, Open Targets, and Cambridge University Hospitals NHS Foundation Trust!
We need new drugs for IBD. Currently, 1 in 123 people suffer from Crohn’s, ulcerative colitis or some form of IBD in the UK, but there is no cure, and existing drugs can be ineffective or lose efficacy over time.
These findings help resolve the biology of IBD, and nominate targets for drug development or repurposing. A similar approach could be applied to other complex diseases to nominate effector genes from GWAS loci.
To test this hypothesis, they generated the largest collection of single-cell RNA sequencing data from IBD-relevant sites (terminal ileum, rectum, blood), resulting in nearly 2.2 million single-cell transcriptomes from over 400 individuals including 125 with IBD.
Genetics are a good starting point for drug development, but while Genome Wide Association Studies have nominated loci for IBD, only a fraction of these have successfully been linked to causal genes with current eQTL discovery methods, which often rely on bulk RNA sequencing of heterogeneous tissues
By mapping eQTLs at three progressively higher resolutions, they found over 84,000 eQTLs in 251 cellular annotations. Notably, many eQTLs were only found at higher resolutions, and cell-type-level eQTLs were more than twice as likely to colocalise with IBD GWAS loci than tissue-level eQTLs.
Mathew Garnett was one of the first group leaders to receive an Open Targets project award.
He discusses how Open Targets projects brings together academic and industry teams in a unique research partnership model.
Find out more: blog.opentargets.org/how-open-tar...
“Open Targets has had the single biggest impact in integrating the @sangerinstitute.bsky.social and @ebi.embl.org science, above and beyond any other initiative I’ve seen in that time." 🤝
Open Targets
@tobioinformatics.bsky.social @bradleyomics.bsky.social hypothesised that colocalising GWAS signals with cell-type-specific single-cell eQTLs would more readily nominate disease effector genes, since regulators active only in specific cellular contexts are more likely to escape purifying selection
Out now in Nature!
Genetic analysis of the largest single-cell dataset of Inflammatory Bowel Disease (IBD)-relevant tissues nominates effector genes and cell types at over half of known IBD loci, including 74 for which this is the first candidate effector gene 🖥️🧬
www.nature.com/articles/s41...
