Genomic analysis of Colombian Leishmania panamensis strains with different level of virulence
| Autor: | Janny Alexander Villa, Omar Triana-Chávez, Hideo Imamura, Juanita Gil, Jean-Claude Dujardin, José R. Ramírez-Pineda, Jorge Duitama, Natalia Muñoz, Juan F. Alzate, Daniel Alfonso Urrea |
|---|---|
| Přispěvatelé: | Clinical sciences, Medical Genetics, Department of Bio-engineering Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Leishmaniasis Mucocutaneous DNA Copy Number Variations Sequence analysis 030106 microbiology Virulence lcsh:Medicine Colombia Genome Polymorphism Single Nucleotide DNA sequencing Article Leishmania braziliensis Machine Learning 03 medical and health sciences Animals Leishmania guyanensis lcsh:Science Gene Biology Comparative genomics Genetics Mice Inbred BALB C Multidisciplinary biology Strain (biology) lcsh:R Sequence Analysis DNA Leishmania biology.organism_classification 030104 developmental biology Female lcsh:Q Human medicine Genome Protozoan |
| Zdroj: | Scientific reports Scientific Reports, Vol 8, Iss 1, Pp 1-16 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|