Journal Article

Analysis of intracellular and intercellular crosstalk from omics data

Chiodi, Alice, Pelucchi, Paride, Mosca, Ettore

2025

Overview

Disease phenotypes can be described as the consequence of interactions among molecular processes that are altered beyond resilience. Here, we address the challenge of assessing the possible alteration of intra- and inter-cellular molecular interactions among processes or cells. We present an approach, designated as “Ulisse”, which complements the existing methods in the domains of enrichment analysis, pathway crosstalk analysis and cell-cell communication analysis. It applies to gene lists that contain quantitative information about gene-related alterations, typically derived in the context of omics or multi-omics studies. Ulisse highlights the presence of alterations in those components that control the interactions between processes or cells. Considering the complexity of statistical assessment of network-based analyses, crosstalk quantification is supported by two distinct null models, which systematically sample alternative configurations of gene-related changes and gene-gene interactions. Further, the approach provides an additional way of identifying the genes associated with the phenotype. As a proof-of-concept, we applied Ulisse to study the alteration of pathway crosstalks and cell-cell communications in triple negative breast cancer samples, based on single-cell RNA sequencing. In conclusion, our work supports the usefulness of crosstalk analysis as an additional instrument in the “toolkit” of biomedical research for translating complex biological data into actionable insights.

• Publisher: Public Library of Science,PLOS,Public Library of Science (PLoS)
• Subject: Biology and Life Sciences / Cell Communication - genetics / Cell interactions / Communication / Communications networks / Complexity / Computer and Information Sciences / Crosstalk / Female / Gene expression / Gene Expression Regulation, Neoplastic / Gene Regulatory Networks / Gene sequencing / Genomics - methods / Genotype & phenotype / Humans / Medical research / Medicine and Health Sciences / Molecular interactions / Multiomics / Phenotypes / Proof of Concept Study / Proteins / Research and Analysis Methods / Signal Transduction - genetics / Single-Cell Gene Expression Analysis / Triple Negative Breast Neoplasms - genetics / Triple Negative Breast Neoplasms - pathology