Clinical genetics articles from across Nature Portfolio

A therapeutic strategy that alters gene expression in a rare and severe neurodevelopmental condition has been tested in stem-cell-based models of the disease, and has been shown to correct genetic and cellular defects.

Pei et al. applied Gaussian process-based machine learning to capture dynamic spatial covariance relationships managed by proteostasis to mediate cooperative folding on a residue basis as a standard model for precision disease management.

A therapeutic strategy that alters gene expression in a rare and severe neurodevelopmental condition has been tested in stem-cell-based models of the disease, and has been shown to correct genetic and cellular defects.

Clinical classification of genomic variants identified on sequencing is often challenging, with many variants classified as Variants of Uncertain Significance (VUS) on account of insufficient evidence. Advances in sequencing and gene synthesis has made feasible multiplexed assays of variant effect (MAVEs), which quantify the functional impact of many thousands of genomic variants in a single experiment. These assays and the functional evidence they generate have the potential to empower more accurate clinical variant classification. However, there are many outstanding challenges and opportunities that require joint resolution and specification, thus necessitating communication between the research scientists who have designed and performed MAVEs and the clinicians and diagnostic scientists who will apply their data to clinical variant classification. In the ‘Clinical Application of MAVE Data’ workshop, held on 12th July 2023 at the Wellcome Connecting Science Conference Centre in between two relevant research meetings, ‘Curating the Clinical Genome 2023’ and the ‘Mutational Scanning Symposium 2023’, 44 key scientific and/or clinical stakeholders were brought together to consider important questions relating to clinical application of MAVE data, such as quantitative validation, variant truth-sets, platforms and standards for dissemination of MAVE data. The outcomes and possible next steps that were discussed encompassed development of focused workshops to develop consensus recommendations, creating a MAVE evaluation working group, and collaboration of ClinVar and MaveDB to enact software changes that support enhanced functional data submission.

Gene-editing strategies that allow stem cells to evade the immune system offer hope for universal cell-replacement therapies.