PhyloQuant approach provides insights into Trypanosoma cruzi evolution using a systems-wide mass spectrometry-based quantitative protein profile

Author(s)

Mule, Simon Ngao ^[1] ; Costa-Martins, Andre Guilherme ^[1] ; Rosa-Fernandes, Livia ^[1] ; de Oliveira, Gilberto Santos ^[1] ; Rodrigues, Carla Monadeli F. ^[1] ; Quina, Daniel ^[1] ; Rosein, Graziella E. ^[2] ; Geraldes Teixeira, Marta Maria ^[1] ; Palmisano, Giuseppe ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

• Document type: Journal article
• Source: COMMUNICATIONS BIOLOGY; v. 4, n. 1 MAR 11 2021.
• Web of Science Citations: 0

Abstract

The etiological agent of Chagas disease, Trypanosoma cruzi, is a complex of seven genetic subdivisions termed discrete typing units (DTUs), Tcl-TcVI and Tcbat. The relevance of T. cruzi genetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution requires understanding the parasite origin and population structure. In this study, we introduce the PhyloQuant approach to infer the evolutionary relationships between organisms based on differential mass spectrometry-based quantitative features. In particular, large scale quantitative bottom-up proteomics features (MS1, iBAQ and LFQ) were analyzed using maximum parsimony, showing a correlation between T. cruzi DTUs and closely related trypanosomes' protein expression and sequence-based clustering. Character mapping enabled the identification of synapomorphies, herein the proteins and their respective expression profiles that differentiate T. cruzi DTUs and trypanosome species. The distance matrices based on phylogenetics and PhyloQuant clustering showed statistically significant correlation highlighting the complementarity between the two strategies. Moreover, PhyloQuant allows the identification of differentially regulated and strain/DTU/species-specific proteins, and has potential application in the identification of specific biomarkers and candidate therapeutic targets. (AU)

• FAPESP's process: 18/13283-4 - Discovery of biomarkers of Chagas' disease in urine using mass spectrometry techniques
• Grantee: Gilberto Santos de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/04032-5 - Dissecting the pathogenesis of Chagas Disease by deep glycomics and glycoproteomics approaches
• Grantee: Simon Ngao Mule
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
• Grantee: Giuseppe Palmisano
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/25494-9 - Trypanosoma Cruzi signaling due to changes in the external conditions: ECM and pH changes
• Grantee: Maria Julia Manso Alves
• Support Opportunities: Regular Research Grants