Modelling reliable metabolic phenotypes by analysing the context-specific transcriptomics data

Genome-scale metabolic models (GEMs) are valuable tools for investigating healthy and disease states, but often lack the specificity to capture context-dependent metabolic adaptations. Tailoring GEMs using transcriptomic data is crucial for studying these context-specific variations by accurately identifying active metabolic reactions. This study introduces an algorithm called 'Localgini', which uses the Gini coefficient to quantify gene expression variability across samples, enabling precise identification of active reactions for context-specific models (CSMs). To evaluate Localgini, CSMs were generated using six different model extraction methods (MeMs) for NCI-60 cancer cell lines and human tissue datasets. Localgini-based CSMs better represent housekeeping functionalities and known metabolic pathways. Moreover, Localgini-generated active reaction sets require minimal support from the MeMs to build the CSMs. Localgini minimizes variability across CSMs built with different MeMs and the same gene expression data. Overall, by incorporating gene expression heterogeneity, Localgini provides an accurate method for constructing CSMs.