Database Commons

a catalog of worldwide biological databases

Trypanosoma cruzi, the causative agent of Chagas disease, poses a significant health challenge due to limited therapeutic options and an incomplete understanding of its biology. Approximately half of the genome encodes hypothetical proteins with unknown functions, underscoring the need for systematic functional annotation. Protein-protein interactions (PPIs) underpin essential cellular processes, yet no large-scale PPI map has been developed for T. cruzi ─a critical gap that impedes both functional annotation of its proteome and drug discovery. This study presents the first comprehensive PPI network for T. cruzi, constructed using quantitative mass spectrometry-based cofractionation data. The network includes 1319 proteins and more than 16,000 predicted interactions, with 47% of the proteins classified as hypothetical, consistent with the 49% hypothetical annotation rate in the proteome. Their placement within functionally enriched network modules provides unprecedented insights into their potential biological roles. Network analysis revealed densely interconnected cores enriched with essential cellular functions. This PPI network exhibits small-world properties, with conserved proteins showing higher connectivity, reinforcing their central roles in the parasite's biology. This resource, publicly available at https://2025.trypsnetdb.org/, offers a powerful platform for exploring T. cruzi biology and prioritizing novel therapeutic targets, revealing central hubs of protein organization, resolving ribosomal and proteasomal complexes, and enabling functional predictions for numerous hypothetical proteins through integrative structural modeling.

Leishmania donovani is the causative agent of visceral leishmaniasis, a tropical disease affecting millions worldwide. While proteomic studies of Leishmania species have been conducted, the organization of protein-protein interaction (PPI) networks in L. donovani remains largely unexplored. Here, we present a protein interaction network for L. donovani generated through size-exclusion chromatography coupled with mass spectrometry (SEC-MS) and computational analysis. We quantified 3468 proteins with high confidence, of which approximately 70 % are conserved across the Tritryps (Trypanosoma brucei, T. cruzi, and L. donovani). The resulting network contains 1509 nodes and 16,095 interactions, exhibiting scale-free topology and covering key cellular machineries such as the proteasome, ribosome, translation initiation complexes, and BBSome. Remarkably, most annotated Leishmania complexes remained intact within the network, highlighting its high quality. Paralogs within L. donovani frequently interacted with each other, a phenomenon observed at a higher rate than reported in different organisms. Beyond structural organization, the network also provided interaction-based evidence that functionally contextualizes previously uncharacterized or poorly annotated proteins. Complexes involved in mRNA metabolism and flagellar assembly revealed novel components supported by conserved interaction patterns, underscoring the biological utility of the network for functional inference. Our study provides the first experimentally derived, large-scale interaction network specific to L. donovani, offering critical insights into the parasite's molecular architecture. All interaction data are available through our dedicated database at https://2025.trypsnetdb.org.

Trypanosomatid parasites cause serious infections in humans and production losses in livestock. Due to the high divergence from other eukaryotes, such as humans and model organisms, the functional roles of many trypanosomatid proteins cannot be predicted by homology-based methods, rendering a significant portion of their proteins as uncharacterized. Recent technological advances have led to the availability of multiple systematic and genome-wide datasets on trypanosomatid parasites that are informative regarding the biological role(s) of their proteins. Here, we report TrypsNetDB (http://trypsNetDB.org), a web-based resource for the functional annotation of 16 different species/strains of trypanosomatid parasites. The database not only visualizes the network context of the queried protein(s) in an intuitive way but also examines the response of the represented network in more than 50 different biological contexts and its enrichment for various biological terms and pathways, protein sequence signatures, and potential RNA regulatory elements. The interactome core of the database, as of Jan 23, 2017, contains 101,187 interactions among 13,395 trypanosomatid proteins inferred from 97 genome-wide and focused studies on the interactome of these organisms.