Institute of Genetics and Cancer

3D confinement reshapes RNA folding and enhances circularization in the Zika virus

Abstract Many RNA molecules function within confined environments, but the effect of confinement on RNA folding remains poorly understood. Proximity ligation experiments reveal altered long-range contacts in confined versus unconfined states, yet they do not explain how spatial c...

Combining MAVEs and computational predictors improves variant classification across ancestries in hereditary cancer genes

Many commonly used computational tools for variant effect prediction exhibit ancestry-related bias because they are trained on clinical or population datasets that under-represent global diversity, leading to uneven and sometimes unfair variant classification across ancestries. M...

Generalisability of an adult-trained AI model to paediatric coeliac disease diagnosis: a multicentre external validation study

Background Coeliac disease diagnosis on duodenal biopsies is limited by interobserver variability. We have previously demonstrated pathologist-level performance with our artificial intelligence (AI) model for the histopathological diagnosis of adult coeliac disease, but not in pa...

Establishing Stakeholder Priorities for Development of a Multi‐Arm Multi‐Stage Platform Trial in Crohn's Disease

ABSTRACT Background and Aims The expanding range of advanced therapies for Crohn's disease (CD) has increased complexity in treatment selection, particularly in refractory disease. Conventional randomised controlled trials are limited in evaluating multiple treatment strategies e...

The moonlighting functions of SEC13 in nonsense-mediated mRNA decay and the regulation of ER stress

ABSTRACT The nonsense-mediated decay pathway (NMD) is an RNA quality control mechanism that regulates the stability of target RNAs. We previously identified the ER-localized SEC13 protein as a novel NMD factor in C. elegans and in HeLa cells; raising the possibility that it could...

Response of the replisome to araA and araC suggests a mechanism for arabinosyl nucleoside tolerance

Arabinosyl (ara) nucleoside analogues such as vidarabine (araA) and cytarabine (araC) are antimetabolites known to inhibit DNA polymerases in isolation. However, their effects on DNA synthesis catalysed by the multi-protein replisome remain unknown. Here, we uncover a central rol...

Why variant effect predictors and multiplexed assays agree and disagree

Abstract Computational variant effect predictors (VEPs) and multiplexed assays of variant effect (MAVEs) are two key tools for assessing the functional consequences of genetic variants. While their outputs are often concordant, there are also many differences. Here, we analyse mi...