Spotiphy finds new insights from spatial transcriptomics data
Peng, who studies neurobiology, explained how single-cell spatial transcriptomics provides an opportunity to understand neurodegenerative diseases better, including Alzheimer’s, especially aberrant cells and their gene expression. However, “previous spatial transcriptomics data for Alzheimer’s have not truly resolved single-cell data,” Peng said. “Existing methods result in a low-resolution output, often clustering multiple cells into a single spot. We merged adjacent sections for RNA analysis and imaging one-to-one with Spotiphy, truly reaching a clean single-cell resolution with high gene coverage.
Applied to a mouse model of Alzheimer’s Disease, Spotiphy confirmed the findings of previous studies, validating the tool’s ability to pinpoint cell location and gene expression patterns accurately. This increased confidence in the technique. In addition, the researchers deployed Spotiphy in new experiments, finding that subsets of astrocytes, a common cell type in the central nervous system, are associated with specific brain regions. They also found that disease-associated microglia, a rare type of immune cells, had a greater presence in brains affected by Alzheimer’s, supporting previous findings that microglial dysfunction may be involved in the disease.
“The real power of this algorithm is its ability to distinguish subtle differences within the same cell type that previous technologies could not detect,” Yu said. “For example, identifying sub-populations of astrocytes located in certain areas of the brain.”
Findings were not limited to neurobiology. The scientists also showed that Spotiphy could be used to analyze other tissues, including cancer samples. The tool successfully identified different spatial domains and alterations in tumor-tumor microenvironment interactions.
“We saw the data reflected known breast cancer heterogeneity,” said co-first author Jiyuan Yang, PhD, St. Jude Department of Computational Biology. “We also invested significant efforts to generating the matched datasets for mouse brains, which we believe will be a valuable resource for the spatial omics community.”
“We’ve made a tool that can resolve single-cell spatial transcriptomics of any given tissue,” Yu said. “In other words, Spotiphy lets scientists see things that they could not see before.”
Spotiphy is freely available at https://github.com/jyyulab/Spotiphy.
Authors and funding
The study’s other co-first author is Ziqian Zheng, University of Wisconsin-Madison. The study’s other co-senior author is Kaibo Liu, University of Wisconsin-Madison. The study’s other authors are Yun Jiao, Kaiwen Yu, Sheetal Bhatara, Xu Yang, Sivaraman Natarajan, John Easton and Koon-Kiu Yan, all of St. Jude; and Jiahui Zhang, University of Wisconsin-Madison.
This work is supported in part by grants from National Institutes of Health (R01GM134382, U01CA264610, U01CA281868, R01CA274251, RF1AG068581 and ALSAC, the fundraising and awareness organization of St. Jude.
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