Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor-immune hubs Journal Article
| Authors: | He, S.; Jin, Y.; Nazaret, A.; Shi, L.; Chen, X.; Rampersaud, S.; Dhillon, B. S.; Valdez, I.; Friend, L. E.; Fan, J. L.; Park, C. Y.; Mintz, R. L.; Lao, Y. H.; Carrera, D.; Fang, K. W.; Mehdi, K.; Rohde, M.; McFaline-Figueroa, J. L.; Blei, D.; Leong, K. W.; Rudensky, A. Y.; Plitas, G.; Azizi, E. |
| Article Title: | Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor-immune hubs |
| Abstract: | Spatially resolved gene expression profiling provides insight into tissue organization and cell-cell crosstalk; however, sequencing-based spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for rigorous interpretation of cell states, mostly do not use associated histology images and are not capable of inferring shared neighborhoods across multiple tissues. Here we present Starfysh, a computational toolbox using a deep generative model that incorporates archetypal analysis and any known cell type markers to characterize known or new tissue-specific cell states without a single-cell reference. Starfysh improves the characterization of spatial dynamics in complex tissues using histology images and enables the comparison of niches as spatial hubs across tissues. Integrative analysis of primary estrogen receptor (ER)-positive breast cancer, triple-negative breast cancer (TNBC) and metaplastic breast cancer (MBC) tissues led to the identification of spatial hubs with patient- and disease-specific cell type compositions and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC. Reference-free integrative analysis of spatial transcriptomics data is achieved with archetype analysis. |
| Keywords: | hypoxia; gene-expression; mesenchymal transition; cancer progression; single-cell |
| Journal Title: | Nature Biotechnology |
| Volume: | 43 |
| Issue: | 2 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-02-01 |
| Start Page: | 223 |
| End Page: | 235 |
| Language: | English |
| ACCESSION: | WOS:001190085400001 |
| DOI: | 10.1038/s41587-024-02173-8 |
| PROVIDER: | wos |
| PMCID: | PMC11415552 |
| PUBMED: | 38514799 |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Alexander Rudensky and George Plitas -- Source: Wos |
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