Patient-Specific Cell Communication Networks Associate With Disease Progression in Cancer

Frontiers in Genetics

Alexander V. Ratushny¹  Boris Aguilar²  David L. Gibbs²  Vésteinn Thorsson²  Ilya Shmulevich² 

[1] Bristol Myers Squibb, Seattle, WA, United States;Institute for Systems Biology, Seattle, WA, United States;

关键词: systems biology;    bioinformatics;    computational oncology;    immuno-oncology;    cell communication;    networks;   

DOI  :  10.3389/fgene.2021.667382

来源: DOAJ

【 摘 要 】

The maintenance and function of tissues in health and disease depends on cell–cell communication. This work shows how high-level features, representing cell–cell communication, can be defined and used to associate certain signaling “axes” with clinical outcomes. We generated a scaffold of cell–cell interactions and defined a probabilistic method for creating per-patient weighted graphs based on gene expression and cell deconvolution results. With this method, we generated over 9,000 graphs for The Cancer Genome Atlas (TCGA) patient samples, each representing likely channels of intercellular communication in the tumor microenvironment (TME). It was shown that cell–cell edges were strongly associated with disease severity and progression, in terms of survival time and tumor stage. Within individual tumor types, there are predominant cell types, and the collection of associated edges were found to be predictive of clinical phenotypes. Additionally, genes associated with differentially weighted edges were enriched in Gene Ontology terms associated with tissue structure and immune response. Code, data, and notebooks are provided to enable the application of this method to any expression dataset (https://github.com/IlyaLab/Pan-Cancer-Cell-Cell-Comm-Net).

【 授权许可】

Unknown