Genomic Analysis of Colombian Leishmania panamensis strains with different level of virulence

ABSTRACT: The establishment of Leishmania infection in mammalian hosts and the subsequent manifestation of clinical symptoms require internalization into macrophages, immune evasion and parasite survival and replication. Although many of the genes involved in these processes have been described, the genetic and genomic variability associated to differences in virulence is largely unknown. Here we present the genomic variation of four Leishmania (Viannia) panamensis strains exhibiting different levels of virulence in BALB/c mice and its application to predict novel genes related to virulence. De novo DNA sequencing and assembly of the most virulent strain allowed comparative genomics analysis with sequenced L. (Viannia) panamensis and L. (Viannia) braziliensis strains, and showed important variations at intra and interspecific levels. Moreover, the mutation detection and a CNV search revealed both base and structural genomic variation within the species. Interestingly, we found differences in the copy number and protein diversity of some genes previously related to virulence. Several machine-learning approaches were applied to combine previous knowledge with features derived from genomic variation and predict a curated set of 66 novel genes related to virulence. These genes can be prioritized for validation experiments and could potentially become promising drug and immune targets for the development of novel prophylactic and therapeutic interventions.

• Autores: Urrea Montes, Daniel Alfonso; Duitama Castellanos, Jorge Alexander; Alzate Restrepo, Juan Fernando; Gil Bedoya, Juanita; Muñoz Durango, Natalia; Villa Pulgarín, Janny Alexander; Ramírez Pineda, José Robinson; Triana Chávez, Omar; Dujardin, Jean Claude; Imamura, Hideo
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2018
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/36543
• Acceso en línea: https://hdl.handle.net/10495/36543
• Palabra clave: Variaciones en el Número de Copia de ADN; DNA Copy Number Variations; Genoma de Protozoos; Genome, Protozoan; Leishmania braziliensis; Leishmania guyanensis; Aprendizaje Automático; Machine Learning; Polimorfismo de Nucleótido Simple; Polymorphism, Single Nucleotide; Ratones Endogámicos; ice, Inbred Strains; Colombia
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/