Comparative Genome-Scale Reconstruction of Gapless Metabolic Networks for Present and Ancestral Species

Background: We introduce novel use cases for our computational approach CoReCo [1] for comparative metabolic re-construction.

Method: The CoReCo method reconstructs genome-scale gapless metabolic networks simultaneously for a large number of species by integrating sequence data in a probabilistic framework. Our comparative approach is particularly useful in scenarios where the quality of available sequence data is lacking, and when reconstructing evolutionary distant species, such as genomes assembled from metagenomics data. Moreover, the reconstructed networks are fully carbon mapped, allowing their use in 13C flux analysis. We have built reaction and reference sequence databases for Bacteria and Fungi by integrating ChEBI, KEGG, Rhea, YMDB and HMDB, and the genome-scale metabolic models of several microorganisms.

Results: We will present results of latest analysis of our bacterial and fungal models. On bacterial side experimental verifications for models built at VTT have been carried out at University of Virginia and CoReCo models have been found to fit well to experimental data. On fungal side we have concentrated on reconstructing a model for the protein production host Trichoderma reesei.

Conclusion: Our reconstruction method allows comparative reconstruction of an arbitrary number of species from sequence and phylogenetic data. In contrast to many existing reconstruction techniques, only minimal manual effort is required before the reconstructed models are usable in flux balance experiments.

[1] Pitkänen et al. (2014). PLoS Computational Biology, 10(2), e1003465.