Scaling metabolic model reconstruction up to the pan-genome level: A systematic review and prospective applications to photosynthetic organisms

Abstract

Advances in genomics technologies have generated large data sets that provide tremendous insights into the genetic diversity of taxonomic groups. However, it remains challenging to pinpoint the effect of genetic diversity on different traits without performing resource-intensive phenotyping experiments. Pan-genome-scale metabolic models (panGEMs) extend traditional genome-scale metabolic models by considering the entire reaction repertoire that enables the prediction and comparison of metabolic capabilities within a taxonomic group. Here, we systematically review the state-of-the-art methodologies for constructing panGEMs, focusing on used tools, databases, experimental datasets, and orthology relationships. We highlight the unique advantages of panGEMs compared to single-species GEMs in predicting metabolic phenotypes and in guiding the experimental validation of genome annotations. In addition, we emphasize the disparity between the available (pan-)genomic data on photosynthetic organisms and their under-representation in current (pan)GEMs. Finally, we propose a perspective for tackling the reconstruction of panGEMs for photosynthetic eukaryotes that can help advance our understanding of the metabolic diversity in this taxonomic group.