Abstract
INTRODUCTION: The availability of large-scale multi-omic data has revolution-ized the study of cellular machinery, enabling a systematic understanding of biological processes. However, the integration of these datasets into Genome-Scale Models of Metabolism (GEMs) re-mains underexplored. Existing methods often link transcriptome and proteome data independently to reaction boundaries, providing models with estimated maximum reaction rates based on individual datasets. This independent approach, however, introduces uncertainties and inaccuracies. METHODS: To address these challenges, we applied a principal component analysis (PCA)-based approach to integrate transcriptome and proteome data. This method facilitates the reconstruction of context-specific models grounded in multi-omics data, enhancing their biological relevance and predictive capacity. RESULTS: Using this approach, we successfully reconstructed an astrocyte GEM with improved prediction capabilities compared to state-of-the-art models available in the literature. DISCUSSION: These advancements underscore the potential of multi-omic inte-gration to refine metabolic modeling and its critical role in studying neurodegeneration and developing effective therapies.