Characterization of Genetic Variability of Venezuelan Equine Encephalitis Viruses

Abstract

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that has caused large outbreaks of severe illness in both horses and humans. New approaches are needed to rapidly infer the origin of a newly discovered VEEV strain, estimate its equine amplification and resultant epidemic potential, and predict human virulence phenotype. We performed whole genome single nucleotide polymorphism (SNP) analysis of all available VEE antigenic complex genomes, verified that a SNP-based phylogeny accurately captured the features of a phylogenetic tree based on multiple sequence alignment, and developed a high resolution genome-wide SNP microarray. We used the microarray to analyze a broad panel of VEEV isolates, found excellent concordance between array- and sequence-based SNP calls, genotyped unsequenced isolates, and placed them on a phylogeny with sequenced genomes. The microarray successfully genotyped VEEV directly from tissue samples of an infected mouse, bypassing the need for viral isolation, culture and genomic sequencing. Finally, we identified genomic variants associated with serotypes and host species, revealing a complex relationship between genotype and phenotype.

A Machine Learning-Based Identification of Genes Affecting the Pharmacokinetics of Tacrolimus Using the DMETTM Plus Platform

“…However, the observed effect of rs1137115 on the systemic exposure to tacrolimus is mechanistically hard to explain and is most likely to be a chance finding because the effect is not consistent by the rs776746 allele (Table S1). rs3814055 (NR1I2) was significantly associated with both C max and AUC last in the false discovery rate (FDR)-adjusted multiple testing analysis and LASSO models in our previous study [13]. However, rs3814055 was identified as a significant genetic variant for AUC last only by the random forest analysis in the present study (Table 2).…”

“…First, our subjects are healthy, not transplanted patients [6,7]. This could be beneficial in that the relationships between genetic variations and tacrolimus pharmacokinetics were not confounded by many disease-related variables, which could not be easily adjusted for in many cases as previously shown [13]. Furthermore, we demonstrate that rs776746 (CYP3A5) is consistently the best predictor of exposure to tacrolimus no matter what machine learning algorithms are used (Tables 1-3).…”

“…A branch denotes a test or set of tests to be performed on a specific property such as genotype while a node indicates a category or class such as phenotype. Decision trees adequately classify patients by their genotypes to diagnose a disease and to predict its prognosis [12][13][14]. Furthermore, random forests integrate or ensemble multiple randomly chosen decision trees, thereby forests, with each decision tree providing an independent classification prediction.…”

Molecular and cellular evidence of natural Venezuelan equine encephalitis virus infection in frugivorous bats in Colombia

“…Venezuelan equine encephalitis virus (VEEV) is a positive-sense virus RNA of the family Togaviridae and the genus Alphavirus, within this same group are the equine encephalitis viruses (EEV) of the East and West, Mayaro, Madariaga, Mucambo, and Everglades [1,2]. Venezuelan equine encephalitis is an emerging infectious disease in Latin America [3,4].…”

Eco-epidemiology of the Venezuelan equine encephalitis virus in bats of Córdoba and Sucre, Colombia

“…The Venezuelan equine encephalitis virus (VEEV) belongs to the genus of alphaviruses (Togaviridae) with enzootic and epizootic serotypes. Within this same group are the equine encephalitis viruses of the East and West, Mayaro, Mucambo and Everglades (Zacks and Paessler, 2010;Gardner et al, 2016). VEEV is an emerging infectious disease in Latin America (Aguilar et al, 2011;Vittor et al, 2016).…”