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X-vine models for multivariate extremes
No full textRegular vine sequences permit the organization of variables in a random vector along a sequence of trees. Vine-based dependence models have become greatly popular as a way to combine arbitrary bivariate copulas into higher-dimensional ones, offering flexibility, parsimony, and tractability. In this project, we use regular vine sequences to decompose and construct the exponent measure density of a multivariate extreme value distribution, or, equivalently, the tail copula density. Although these densities pose theoretical challenges due to their infinite mass, their homogeneity property offers simplifications. The theory sheds new light on existing parametric families and facilitates the construction of new ones, called X-vines. Computations proceed via recursive formulas in terms of bivariate model components. We develop simulation algorithms for X-vine multivariate Pareto distributions as well as methods for parameter estimation and model selection on the basis of threshold exceedances. The methods are illustrated by Monte Carlo experiments and a case study on US flight delay data.</p
Conserved and distinct expression of circular RNAs in commercially used Marek’s disease vaccine viruses
No full textCircular RNAs (circRNAs) are covalently closed RNA molecules, supporting a wide diversity of functions. While aberrant circRNA expression stands as a recognized hallmark of cancer development, our attention has turned to investigating their role in viral infections, specifically Mardivirus Gallidalpha 2 (GaHV-2, Marek’s disease virus) infection. In a previous study focused on the virulent GaHV-2 strain, RB-1B, we extensively catalogued circRNAs produced from virulence genes, notably from the MEQ-vIL-8 locus and the latency-associated transcripts (LATs) gene. Building upon this groundwork, our current investigation uncovers novel loci expressing viral circRNAs in distinct stages of GaHV-2 infection. Furthermore, we extend our focus to viral circRNA signatures in three commonly used Marek’s disease vaccines, the avirulent GaHV-2 (CVI988/Rispens strain), non-oncogenic Mardivirus Gallidalpha 3 (GaHV-3) and non-oncogenic Mardivirus Meleagridalpha 1 (MeHV-1) commercially called herpesvirus of turkey. In these vaccine viruses, we identified viral circRNA expression from a locus antisense to the ICP4 immediate early gene, a conserved feature across the three species. This region has been characterized herein for the first time in terms of candidate LATs’ exons and introns for GaHV-3 and MeHV-1. LATs’ circRNAs were then deeply analysed, and we observed both similarities and distinctions when compared with those of the virulent GaHV-2. Another conserved gene, encoding the DNA packaging protein, was identified as a source of circRNAs in all three species. Eventually, different levels of circRNAs were found to be expressed from the meq locus between virulent and avirulent GaHV-2 strains. Our findings highlight a conserved pattern of virus-derived circRNAs in these related avian alphaherpesviruses. This conservation underscores the potential significance of these transcripts in completing the viral cycle and facilitating viral spread.</p