STMiner: Gene-centric spatial transcriptomics for deciphering tumor tissues

Cell Genomics, vol. 5, pp. 100771

Abstract

Analyzing spatial transcriptomics data from tumor tissues poses several challenges beyond those of healthy samples, including unclear boundaries between different regions, uneven cell densities, and relatively higher cellular heterogeneity. Collectively, these bias the background against which spatially variable genes are identified, which can result in misidentification of spatial structures and hinder potential insight into complex pathologies. To overcome this problem, STMiner leverages 2D Gaussian mixture models and optimal transport theory to directly characterize the spatial distribution of genes rather than the capture locations of the cells expressing them (spots). By effectively mitigating the impacts of both background bias and data sparsity, STMiner reveals key gene sets and spatial structures overlooked by spot-based analytic tools, facilitating novel biological discoveries. The core concept of directly analyzing overall gene expression patterns also allows for a broader application beyond spatial transcriptomics, positioning STMiner for continuous expansion as spatial omics technologies evolve.

Authors 10

1. Peisen Sun

   Xi'an Jiaotong University

   Affiliation as printed

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

2. Stephen J. Bush

   Xi'an Jiaotong University

   Affiliation as printed

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

3. Songbo Wang

   Xi'an Jiaotong University

   Affiliation as printed

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

4. Mingxuan Li

   Xi'an Jiaotong University

   Affiliation as printed

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

5. Tun Xu

   Xi'an Jiaotong University

   Affiliation as printed

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

6. Pengyu Zhang

   Xi'an Jiaotong University

   Affiliation as printed

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

7. Chengyao Wang

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Department of Endocrinology, Genome Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

8. Linfeng Xu

   Xi'an Jiaotong University

   Affiliation as printed

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

9. Tingjie Wang

   Zhengzhou University

   Affiliation as printed

   The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China

10. Kai Ye corresponding Aachen Faculty of Science, Leiden University

    Leiden University · First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

    Affiliation as printed

    School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China; Department of Gynecology and Obstetrics, Center for Mathematical Medical, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Genome Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Faculty of Science, Leiden University, Leiden, the Netherlands. Electronic address: kaiye@xjtu.edu.cn

    Department of Gynecology and Obstetrics, Center for Mathematical Medical, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

    Faculty of Science, Leiden University, Leiden, the Netherlands

    Genome Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

    MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China

    School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China