New AI tool detects hidden warning signs of disease

Researchers say a closer look inside cells could be used by physicians to detect diseases earlier and better match patients to therapies McGill University researchers have developed an artificial intelligence tool that can detect previously invisible disease markers inside single cells. In a study published in Nature Communications, the researchers demonstrate how the tool, called DOLPHIN, could one day be used by doctors to catch diseases earlier and guide treatment options. “This tool has the potential to help doctors match patients with the therapies most likely to work for them, reducing trial-and-error in treatment,” said senior author Jun Ding, assistant professor in McGill’s Department of Medicine and a junior scientist at the Research Institute of the McGill University Health Centre. Zooming in on genetic building blocks Disease markers are often subtle changes in RNA expression that can indicate when a disease is present, how severe it may become or how it might respond to treatment. Conventional gene-level methods of analysis collapse these markers into a single count per gene, masking critical variation and capturing only the tip of the iceberg, said the researchers. Now, advances in artificial intelligence have made it possible to capture the fine-grained complexity of single-cell data. DOLPHIN moves beyond gene-level, zooming in to see how genes are spliced together from smaller pieces called exons to provide a clearer view of cell states. “Genes are not just one block, they’re like Lego sets made of many smaller pieces,” said first author Kailu Song, a PhD student in McGill’s Quantitative Life Sciences program. “By looking at how those pieces are connected, our tool reveals important disease markers that have long been overlooked.” In one test case, DOLPHIN analyzed single-cell data from pancreatic cancer patients and found more than 800 disease markers missed by conventional tools. It was able to distinguish patients with high-risk, aggressive cancers from those with less severe cases, information that would help doctors choose the right treatment path. A step toward ‘virtual cells’ More broadly, the breakthrough lays the foundation for achieving the long-term goal of building digital models of human cells. DOLPHIN generates richer single-cell profiles than conventional methods, enabling virtual simulations of how cells behave and respond to drugs before moving to lab or clinical trials, saving time and money. The researchers’ next step will be to expand the tool’s reach from a few datasets to millions of cells, paving the way for more accurate virtual cell models in the future. About the study “DOLPHIN advances single-cell transcriptomics beyond gene level by leveraging exon and junction reads” by Kailu Song and Jun Ding et al., was published in Nature Communications. This research was supported by the Meakins-Christie Chair in Respiratory Research, the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Fonds de recherche du Québec.