TROPIC: An Integrative Approach Aimed at Identifying Drug Targetable Human- Parasite Interactions

This project was built upon the previously generated human-parasite PPI networks of 15 eukaryotic parasites, predicted by Dr. Cuesta-Astroz through the pipeline they developed for orthology-based host-pathogen protein-protein interactome identification (Cuesta-Astroz, Santos, Oliviera, & Jensen, 2019).

The Cuesta-Astroz Team reviewed these interaction data through proteome filtering to prioritize potentially interacting proteins. In summary, the pipeline consists of the following steps: filtration of parasite proteins by secretome and membrane localization (based on whether the parasite is unicellular or multicellular), filtration of host proteins by tissue expression, and using STRING to perform an orthology-based mapping of intraspecies interactions to host-parasite pairs. The pipeline concentrates on domain-domain and domain-motif interactions of the protein-protein complexes yielded by the previous filters to prioritize the protein-protein interactions that are more possibly physically obtainable.

The dataset originally included 280 domain-domain interfaces from 15 distinct human-parasite interactions; however, four pairs that were longer than the 1500-sequence limit were removed because they couldn’t be modeled using AF2 v2 on TRUBA resources. The resulting dataset consists of interacting domains of 276 protein-protein complexes selected at the most central nodes of 15 eukaryotic parasites (T. spiralis, T. gondii, T. brucei, S. mansoni, P. vivax, P. knowlesi, L. infantum, L. donovani, L. braziliensis, C. parvum, G. lamblia, T. cruzi, P. falciparum, C. hominis, and L. mexicana) and handed to us by Dr. Cuesta-Astroz under our bilateral funded project called “TROPIC: An integrative approach to define druggable human-parasite interactions” funded by TÜBİTAK and MINCIENCIAS (TÜBİTAK Project No:120N799).