Dr. Yang Jian, leader of the team that published the Nature article unveiling a new method known simply as "gsMap" Photo: courtesy of Westlake University
A Chinese research team unveiled a new method known simply as "gsMap," like a "navigation map" which can identify cells and their spatial patterns associated with complex disorders like schizophrenia and depression, shedding light on the exploration of targeted treatment.
The team from the School of Life Sciences at Westlake University encapsulated the gsMap algorithm as open-source software in their published
Nature article, making this innovative method accessible to scientists worldwide, the Global Times learned from Westlake University on Thursday.
According to the team, psychiatric disorders currently affect hundreds of millions worldwide, yet even cutting-edge medical imaging struggles to pinpoint their root causes. Many complex diseases lack visible markers like plaques or nodules, making it difficult to localize affected cells, a key challenge in precision medicine, the team explained.
"Human traits, from coffee preferences to height, weight, and disease susceptibility, are largely influenced by genetic variations," Dr. Yang Jian, the team leader, explained to the Global Times.
"In the past, scientists worldwide have successfully identified a vast number of genetic variants associated with complex diseases and human traits through genome-wide association studies (GWAS). However, this technology cannot explain how these variants influence the onset and progression of diseases through specific cell types in the human body."
Each cell carries a unique set of actively expressed marker genes, akin to an ID card, that defines its type, state, and spatial location, Yang explained.
The team utilized spatial transcriptomics (ST), an emerging technology that acts as a cellular "map," identifying cell types and their original tissue locations.
By combining GWAS and ST, they sought to answer: Do disease-related genes act uniformly across the body? "GWAS connects diseases to genes, and ST links genes to cell locations. We aimed to bridge diseases and cells via genes," Yang told the Global Times.
This approach transformed the "map" into a "navigation map" capable of pinpointing disease-related cells.
Through extensive refinement and debugging, the team developed gsMap, an innovative data analysis model. This "navigation map" not only identifies cell types associated with complex diseases but also tracks their precise locations within the human body.
Using gsMap, the team discovered that both schizophrenia and depression are significantly linked to glutamatergic neurons. However, the distribution of these neurons varies depending on the disease.
The glutamatergic neurons associated with schizophrenia are predominantly distributed in the cerebral cortex and hippocampus, regions that are closely adjacent to, or even overlap with, areas linked to intelligence.
Further analysis revealed that within the elongated CA1 region of the hippocampus, the correlation between glutamatergic neurons and schizophrenia increases linearly as the neurons approach the dorsal side.
In depression, glutamatergic neurons are concentrated in the midbrain and deep medial prefrontal cortex. By cross-referencing existing drug databases, the team found that genes active in these regions overlap significantly with those targeted by psychiatric drugs, 16 times more than in other cortical areas. This highlights the potential role of these brain regions in depression intervention and targeted therapy.
"These findings expand our understanding of psychiatric disorders and open new pathways for drug development and treatment. By pinpointing the cells where susceptibility genes are actively expressed, we can deliver drugs more precisely to the relevant cells, enhancing efficacy, reducing side effects, and prolonging therapeutic effects," Yang said.
"This research also advances drug development, where delivery mechanisms are just as crucial as efficacy. The pharmaceutical industry is currently advancing small molecules, peptides, antibodies, and even RNA-based drugs, pinpointing the most relevant cells enables the design of more precise, cell-targeted treatments," Yang added.
