Expanding kinetoplastid genome annotation through protein structure comparison

Trinidad Barnech, Juan Manuel - Sotelo-Silveira, José Roberto - Fernández Do Porto, Dario - Smircich, Pablo

Resumen:

Kinetoplastids belong to the Discoba supergroup, an early divergent eukaryotic clade. Although the amount of genomic information on these parasites has grown substantially, assigning gene functions through traditional sequence-based homology methods remains challenging. Recently, significant advancements have been made in in-silico protein structure prediction and algorithms for rapid and precise large-scale protein structure comparisons. In this work, we developed a protein structure-based homology search pipeline (ASC, Annotation by Structural Comparisons) and applied it to transfer biological information to all kinetoplastid proteins available in TriTrypDB, the reference database for this lineage. Our pipeline enabled the assignment of structural similarity to a substantial portion of kinetoplastid proteins, improving current knowledge through annotation transfer. Additionally, we identified structural homologs for representatives of 6,700 uncharacterized proteins across 33 kinetoplastid spe- cies, proteins that could not be annotated using existing sequence-based tools and databases. As a result, this approach allowed us to infer potential biological information for a considerable number of kinetoplastid proteins. Among these, we identified structural homologs to ubiquitous eukaryotic proteins that are challenging to detect in kinetoplastid genomes through standard genome annotation pipelines. The results (KASC, Kinetoplastid Annotation by Structural Comparison) are openly accessible to the community at kasc.fcien.edu.uy through a user-friendly, gene-by-gene interface that enables visual inspection of the data.

Detalles Bibliográficos
2025
ANII: FCE_1_2023_1_176426
Kinetoplastids
Genome annotation
Protein domains
Protein structure comparison
Protein structure
Protein structure databases
RNA structure
Protein structure prediction
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/54085
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)