{"title":"Unveiling fine-scale spatial structures and amplifying gene expression signals in ultra-large ST slices with HERGAST","authors":"Yuqiao Gong, Xin Yuan, Qiong Jiao, Zhangsheng Yu","doi":"10.1038/s41467-025-59139-w","DOIUrl":null,"url":null,"abstract":"<p>We propose HERGAST, a system for spatial structure identification and signal amplification in ultra-large-scale and ultra-high-resolution spatial transcriptomics data. To handle ultra-large spatial transcriptomics (ST) data, we consider the divide and conquer strategy and devise a Divide-Iterate-Conquer framework especially for spatial transcriptomics data analysis, which can also be adopted by other computational methods for extending to ultra-large-scale ST data analysis. To tackle the potential over-smoothing problem arising from data splitting, we construct a heterogeneous graph network to incorporate both local and global spatial relationships. In simulations, HERGAST consistently outperforms other methods across all settings with more than a 10% increase in average adjusted rand index (ARI). In real-world datasets, HERGAST’s high-precision spatial clustering identifies <i>SPP1+</i> macrophages intermingled within colorectal tumors, while the enhanced gene expression signals reveal unique spatial expression patterns of key genes in breast cancer.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"72 1","pages":""},"PeriodicalIF":14.7000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-59139-w","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
We propose HERGAST, a system for spatial structure identification and signal amplification in ultra-large-scale and ultra-high-resolution spatial transcriptomics data. To handle ultra-large spatial transcriptomics (ST) data, we consider the divide and conquer strategy and devise a Divide-Iterate-Conquer framework especially for spatial transcriptomics data analysis, which can also be adopted by other computational methods for extending to ultra-large-scale ST data analysis. To tackle the potential over-smoothing problem arising from data splitting, we construct a heterogeneous graph network to incorporate both local and global spatial relationships. In simulations, HERGAST consistently outperforms other methods across all settings with more than a 10% increase in average adjusted rand index (ARI). In real-world datasets, HERGAST’s high-precision spatial clustering identifies SPP1+ macrophages intermingled within colorectal tumors, while the enhanced gene expression signals reveal unique spatial expression patterns of key genes in breast cancer.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.