Proximogram-A multi-omics network-based framework to capture tissue heterogeneity integrating single-cell omics and spatial profiling

Comput Biol Med. 2024 Nov:182:109082. doi: 10.1016/j.compbiomed.2024.109082. Epub 2024 Sep 9.

Abstract

The increasing availability of patient-derived multimodal biological data for various diseases has opened up avenues for finding the optimal methods for jointly leveraging the information extracted in a customizable and scalable manner. Here, we propose the Proximogram, a graph-based representation that provides a joint construct for embedding independently obtained omics and spatial data. To evaluate the representation, we generated proximograms from 2 distinct biological sources, namely, multiplexed immunofluorescence images and single-cell RNA-seq data obtained from patients across two pancreatic diseases that include normal and chronic Pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). The generated proximograms were used as inputs to 2 distinct graph deep-learning models. The improved classification results over simpler spatial-data-based input graphs point to the increased discriminatory power obtained by integrating structural information from single-cell ligand-receptor signaling data and the spatial architecture of cells in each disease class, which can help point to markers of high diagnostic significance.

Keywords: Graph convolutional networks: GCN; Graph theory; Omics; Pancreatic cancer; Spatial analysis.

MeSH terms

  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Deep Learning
  • Humans
  • Multiomics
  • Pancreas / metabolism
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatitis, Chronic / genetics
  • Pancreatitis, Chronic / metabolism
  • Single-Cell Analysis* / methods