GTADC: A Graph-Based Method for Inferring Cell Spatial Distribution in Cancer Tissues

Biomolecules. 2024 Apr 3;14(4):436. doi: 10.3390/biom14040436.

Abstract

The heterogeneity of tumors poses a challenge for understanding cell interactions and constructing complex ecosystems within cancer tissues. Current research strategies integrate spatial transcriptomics (ST) and single-cell sequencing (scRNA-seq) data to thoroughly analyze this intricate system. However, traditional deep learning methods using scRNA-seq data tend to filter differentially expressed genes through statistical methods. In the context of cancer tissues, where cancer cells exhibit significant differences in gene expression compared to normal cells, this heterogeneity renders traditional analysis methods incapable of accurately capturing differences between cell types. Therefore, we propose a graph-based deep learning method, GTADC, which utilizes Silhouette scores to precisely capture genes with significant expression differences within each cell type, enhancing the accuracy of gene selection. Compared to traditional methods, GTADC not only considers the expression similarity of genes within their respective clusters but also comprehensively leverages information from the overall clustering structure. The introduction of graph structure effectively captures spatial relationships and topological structures between the two types of data, enabling GTADC to more accurately and comprehensively resolve the spatial composition of different cell types within tissues. This refinement allows GTADC to intricately reconstruct the cellular spatial composition, offering a precise solution for inferring cell spatial composition. This method allows for early detection of potential cancer cell regions within tissues, assessing their quantity and spatial information in cell populations. We aim to achieve a preliminary estimation of cancer occurrence and development, contributing to a deeper understanding of early-stage cancer and providing potential support for early cancer diagnosis.

Keywords: cancer; cell type identification; graph attention networks; single-cell RNA sequencing; spatial transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deep Learning
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Single-Cell Analysis* / methods
  • Transcriptome / genetics