In a groundbreaking study, researchers at the University of São Paulo have developed a computational pipeline that has brought us closer to understanding some of the most enigmatic components of the Trypanosoma cruzi proteome. Their work, examining the role of conserved hypothetical proteins in the causative agent of Chagas disease, is published in the latest issue of Advances in Protein Chemistry and Structural Biology.
Filling the Knowledge Gap in Trypanosoma cruzi
Chagas disease remains a significant public health challenge, affecting millions globally. It’s caused by the protozoan parasite Trypanosoma cruzi, an organism which until now, has concealed much of its protein function from scientific scrutiny. Remarkably, about 99.8% of its proteome—the entire set of proteins expressed by an organism—has not been manually annotated, leaving a vast sea of unreviewed proteins, including more than a quarter being conserved hypothetical proteins (CHPs). CHPs are found across various species and evolutionary lineages but lack any established functional understanding.
The study, led by scientists Janaina Macedo-da-Silva, Simon Ngao Mule, Livia Rosa-Fernandes, and Giuseppe Palmisano, harnessed public proteomic data to develop a bioinformatics approach aimed at inferring the biological functions of these CHPs.
The Investigation into the Elusive Proteome
The team’s strategy involved identifying proteins that were differentially expressed in two life stages of the parasite—epimastigote and metacyclic trypomastigote stages—and then characterizing these CHPs by employing a manifold learning technique for dimension reduction and 3D structure homology analysis, known as Spalog.
Through this process, they highlighted 25 and 26 proteins upregulated in the epimastigote and metacyclic trypomastigote stages, respectively, including 18 CHPs (8 and 10 in each stage, respectively). The findings not only align with but also enhance the current literature and functional analyses of the differentially regulated proteins at each stage of the Trypanosoma cruzi life cycle.
Crucially, assigning potential functions to these CHPs, which are often identified in proteomic studies, expands our understanding of Trypanosoma cruzi’s biology. As emphasized by the authors, experimental validation will be necessary to deepen this knowledge and confirm the inferred protein functions.
Towards a Future without Chagas Disease
This investigation opens a pathway to potentially revolutionary findings in the fight against Chagas disease. By elucidating protein functions, researchers can target new drugs, vaccines, or diagnostic tools to curb the spread of the disease that currently affects millions of people, predominantly in Latin America.
Publication and Collaboration
The full study, entitled “A computational pipeline elucidating functions of conserved hypothetical Trypanosoma cruzi proteins based on public proteomic data,” is available in Advances in Protein Chemistry and Structural Biology, volume 138, pages 401-428. The DOI for this significant work is 10.1016/bs.apcsb.2023.07.002.
This research was the result of a collaboration between the GlycoProteomics Laboratory at the Department of Parasitology of the University of São Paulo, the Centre for Motor Neuron Disease Research at Macquarie Medical School, and the School of Natural Sciences at Macquarie University.
References
1. Macedo-da-Silva, J. J., Mule, S. N., Rosa-Fernandes, L., & Palmisano, G. (2024). A computational pipeline elucidating functions of conserved hypothetical Trypanosoma cruzi proteins based on public proteomic data. Advances in Protein Chemistry and Structural Biology, 138, 401-428. doi: 10.1016/bs.apcsb.2023.07.002
2. Herwaldt, B. L. (2018). Epidemiology of Chagas Disease in Non-Endemic Countries: The Role of International Travel and Migration. Archives of Medical Research, 49(1), 76-84.
3. Bern, C. (2015). Chagas’ Disease. The New England Journal of Medicine, 373(5), 456-466.
4. Schmunis, G. A., & Yadon, Z. E. (2010). Chagas disease: A Latin American health problem becoming a world health problem. Acta Tropica, 115(1-2), 14-21.
5. Engman, D. M., & Leon, J. S. (2002). Pathogenesis of Chagas heart disease: role of inflammatory and immune mechanisms. Progress in Cardiovascular Diseases, 44(6), 461-472.
Keywords
1. Trypanosoma cruzi proteome
2. Chagas disease research
3. Conserved hypothetical proteins
4. Functional proteomics
5. Bioinformatics pipeline in parasitology
This study not only aids the global health community in tackling Chagas disease but also exemplifies the power of computational biology in unveiling the secrets of complex diseases. It stands as a testimony to the ongoing quest to uncover the mysteries of pathogens and ultimately to safeguard human health from such insidious diseases.