Comparative Genomics and Network Modeling of Parasites
Conference on Constraint-Based Reconstruction and Analysis (COBRA)
2018
5th Conference on Constraint-Based Reconstruction and Analysis (COBRA 2018)
Poster Session
Poster Session
Sunday, October 14, 2018 - 6:00pm to 7:00pm
To address this challenge, we generated metabolic reconstructions from 160 parasite genomes, representing 38 genera and 111 species. Unsurprisingly, one of the largest genomes (Chromera velia) has the most unique reactions (35); however, the smallest genome (Plasmodium billcollinsi) has six unique reactions. Reconstruction and genome sizes are correlated, but even small networks contain unique features. We next applied our novel automated curation approach to leverage manual curation to improve reconstructions for related organisms. We used these semi-curated reconstructions to compare metabolic capacity and pathway utilization and generate hypotheses about species-specific functions. Here, we focus on the most lethal malaria parasite, Plasmodium falciparum, and the mouse model of severe malaria, P. berghei. For example, while P. falciparum grows in anucleated host erythrocytes, berghei prefers nucleated reticulocytes; in silico, P. falciparum has a reduced demand for host purines when compared to P. berghei, perhaps explaining this host cell preference and highlighting a pathway for which P. berghei is a poor model organism for P. falciparum antimalarial development. By performing these analyses with all 160 reconstructions, we developed a framework to identify metabolic discrepancies and commonalities between genera and species, facilitating comparison of experimental findings and optimizing model system selection to develop therapeutics for parasitic diseases.