A new screening tool has been developed that will investigate the mechanisms behind conditions such as cancer, arthritis, neurodegeneration and cardiovascular disease.
Wellcome Sanger Institute researchers and their collaborators at Open Targets and EMBL’s European Bioinformatics Institute (EMBL-EBI) have developed the screening tool called scSNV-seq.
The tool has been designed to uncover how genetic changes affect gene activity that can lead to diseases such as cancer, autoimmunity, cardiovascular disease and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
The tool enables the investigation of thousands of DNA mutations identified by genetic studies in one experiment, and will help to guide the development of advanced diagnostics and treatments.
scSNV-seq allows the rapid assessment of the impact of thousands of genetic changes in cells that have never been screened before, directly connecting these changes to how those same cells operate.
This technique helps researchers to pinpoint mutations that contribute to disease, which will offer crucial insights for developing targeted therapies.
In a new study, published in Genome Biology, the team applied scSNV-seq to the blood cancer gene, JAK1, accurately assessing the impact of JAK1 mutations.
The assessment revealed for the first time that certain mutations caused a “halfway house” phenotype cycling between different states which was not possible under previous approaches.
The technique is designed to demonstrate versatility across cell types, including hard-to-culture primary cells like T cells and stem-cell derived neurons, as well as various editing methods such as base editing and prime editing.
Applied on a large scale, scSNV-seq could transform understanding of the genetic changes driving cancer and decoding genetic risk for Alzheimer’s, arthritis, diabetes and other complex diseases.
Dr Sarah Cooper, first author of the study at the Wellcome Sanger Institute, stated: “In an era where the rate of genetic variant discovery outpaces our ability to interpret their effects, scSNV-seq fills a major gap for studying challenging cells like T cells and neurons.
“We are already using it to shed light on the impact of Alzheimer’s and Parkinson’s risk variants on brain cells.”
Dr Andrew Bassett, senior author of the study at the Wellcome Sanger Institute, said: “Our technique is able to directly connect effects of mutations to how a cell behaves, revealing downstream impacts that previous technologies alone cannot deliver.
“The technique speeds up the identification of causal genetic mutations, which will allow better diagnosis and deepens our molecular understanding of diseases, paving the way for more targeted and effective treatments.”
