CpG di-nucleotide Odds Ratio Measures Drive Unsupervised Clustering to Characterize the Andes Hantavirus

Abstract Hantaviruses belong to the Bunyaviridae family with small mammals hosting them. Humans are infected either by inhaling virus-containing aerosols or through contact with animal droppings. Even if rodents host the pathogenic species and humans are dead-end hosts, they still get accidentally infected. The Andes Orthohantavirus (ANDV) seems to be the only species with documented person-to-person transmission. Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS) are both serious syndromes associated with hantavirus infections. For both syndromes, the mortality rate is near 40%. Decades of studies have already highlighted the CpG repression in RNA viruses, and both the estimation of the CpG odds ratio and the correlation with their genome polarity were dominant factors in figuring out the CpG bias. We conducted the differential analysis of the CpG odds ratio for all the orthohantaviruses on the full segmented genomes (L, M, S). The results suggested the statistical significance of the three groups. The “Small” genomes were more informative from the CpG odd ratio point of view. We calculated the CpG odds ratio for all the Orthohantaviruses within these segments and furthermore estimated the correlation coefficient with the relative coding sequences (CDS). Preliminary results first confirmed the CpG odds ratio as the lowest among all the nucleotides. Second, the Andes virus was highlighted as the one with the highest CpG odds ratio within CDS. The use of these two measures as features for unsupervised clustering algorithms has allowed us to identify four different sub-groups within the Orthohantaviridae family. The evidence is that the Andes Hantavirus exhibits a peculiar CpG odds ratio distribution, probably linked to its unique characteristic of passing from person to person.