scFASTCORMICS: A Contextualization Algorithm to Reconstruct Metabolic Multi-Cell Population Models from Single-Cell RNAseq Data

Abstract

Tumours are composed of various cancer cell populations with different mutation profiles, phenotypes and metabolism that cause them to react to drugs in diverse manners. Increasing the resolution of metabolic models based on single-cell expression data will provide deeper insight into such metabolic differences and improve the predictive power of the models. scFASTCORMICS is a network contextualization algorithm that builds multi-cell population genome-scale models from single-cell RNAseq data. The models contain a subnetwork for each cell population in a tumour, allowing to capture metabolic variations between these clusters. The subnetworks are connected by a union compartment that permits to simulate metabolite exchanges between cell populations in the microenvironment. scFASTCORMICS uses Pareto optimization to simultaneously maximise the compactness, completeness and specificity of the reconstructed metabolic models. scFASTCORMICS is implemented in MATLAB and requires the installation of the COBRA toolbox, rFASTCORMICS and the IBM CPLEX solver.

Unlocking the potential of T‐cell metabolism reprogramming: Advancing single‐cell approaches for precision immunotherapy in tumour immunity

“…Notably, the significant upregulation of glutamine metabolism, associated with the activation of the transforming growth factor‐β (TGF‐β) signalling pathway, leads to a reduction in the expression of the tissue‐resident marker CD103 on Texs and induces T‐cell apoptosis and impairment 89 . Nevertheless, in the colorectal cancer microenvironment, glutamine not only enhances CD8+ T‐cell glycolysis and lactate metabolism but also serves as an essential nutrient for cytokine synthesis 90 . Thus, the balance of glutamine metabolism is crucial for maintaining T‐cell stability and promoting positive differentiation.…”

“… 89 Nevertheless, in the colorectal cancer microenvironment, glutamine not only enhances CD8+ T‐cell glycolysis and lactate metabolism but also serves as an essential nutrient for cytokine synthesis. 90 Thus, the balance of glutamine metabolism is crucial for maintaining T‐cell stability and promoting positive differentiation.…”

Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures

“…To avoid the manual compilation of different datasets for the identification of core reactions, FASCTORE was recently extended to allow direct integration of high-throughput transcriptomics data. While FASTCORMICS [ 41 ] presents a pipeline for the direct integration of microarray data, rFASTCORMICS [ 42 ] presents another FASCTORE adaptation for the direct integration of RNA-seq data (rFASTCORMICS), and scFASTCORMICS for the integration of single-cell RNA-seq (scRNA-seq) data [ 55 ].…”

“…One of the main limitations of MBA-like methods is that they require a set of core reactions, which need to be compiled manually, while relying on the literature data, biochemical databases, and experimental data. This problem can be at least partially avoided using the FASTCORE extensions that allow direct integration of transcriptomics data [ 41 , 42 , 55 ].…”