Total Ortholog Median Matrix as an alternative unsupervised approach for phylogenomics based on evolutionary distance between protein coding genes

The increasing number of available genomic data allowed the development of phylogenomic analytical tools. Current methods compile information from single gene phylogenies, whether based on topologies or multiple sequence alignments. Generally, phylogenomic analyses elect gene families or genomic regions to construct phylogenomic trees. Here, we presented an alternative approach for Phylogenomics, named TOMM (Total Ortholog Median Matrix), to construct a representative phylogram composed by amino acid distance measures of all pairwise ortholog protein sequence pairs from desired species inside a group of organisms. The procedure is divided two main steps, (1) ortholog detection and (2) creation of a matrix with the median amino acid distance measures of all pairwise orthologous sequences. We tested this approach within three different group of organisms: Kinetoplastida protozoa, hematophagous Diptera vectors and Primates. Our approach was robust and efficacious to reconstruct the phylogenetic relationships for the three groups. Moreover, novel branch topologies could be achieved, providing insights about some phylogenetic relationships between some taxa.

Viral genetic diversity and protective efficacy of a tetravalent dengue vaccine in two phase 3 trials

Two phase 3 placebo-controlled trials of the CYD-TDV vaccine, evaluated in children aged 2−14 y (CYD14) and 9−16 y (CYD15), demonstrated vaccine efficacy (VE) of 56.5% and 60.8%, respectively, against symptomatic virologically confirmed dengue (VCD). Sieve analyses were conducted to evaluate whether and how VE varied with amino acid sequence features of dengue viruses (DENVs). DENV premembrane/envelope amino acid sequences from VCD endpoint cases were aligned with the vaccine insert sequences, and extensions of the proportional hazards model were applied to assess variation in VE with amino acid mismatch proportion distances from vaccine strains, individual amino acid residues, and phylogenetic genotypes. In CYD14, VE against VCD of any serotype (DENV-Any) decreased significantly with increasing amino acid distance from the vaccine, whereas in CYD15, VE against DENV-Any was distance-invariant. Restricting to the common age range and amino acid distance range between the trials and accounting for differential VE by serotype, however, showed no evidence of VE variation with distance in either trial. In serotype-specific analyses, VE against DENV4 decreased significantly with increasing amino acid distance from the DENV4 vaccine insert and was significantly greater against residue-matched DENV4 at eight signature positions. These effects were restricted to 2- to 8-y-olds, potentially because greater seropositivity of older children at baseline might facilitate a broader protective immune response. The relevance of an antigenic match between vaccine strains and circulating DENVs was also supported by greater estimated VE against serotypes and genotypes for which the circulating DENVs had shorter amino acid sequence distances from the vaccine.

Evolutionary dynamics of GII.17 norovirus

Background During the winter of 2014–2015, a rarely reported norovirus (NoV) genotype GII.17 was found to have increased its frequency in norovirus outbreaks in East Asia, surpassing the GII.4 NoV infections. GII.17 genotype has been detected for over three decades in the world. The aim of this study is to examine the evolutionary dynamics of GII.17 over the last four decades. Methods NoV GII.17 sequences with complete or nearly complete VP1 were downloaded from GenBank and the phylogenetic analyses were then conducted. Results The maximum likelihood analysis showed that GII.17 genotype could be divided into four different clades (Clades A–D). The strains detected after 2012, which could be the cause of the outbreaks, were separated into Clades C–D with their mean amino acid distance being 4.5%. Bayesian Markov chain Monte Carlo analyses indicated that the rate of nucleotide substitution per sites was 1.68 × 10−3 nucleotide substitutions/site/year and the time of the most recent common ancestor was 1840. The P2 subdomain of GII.17 was highly variable with 44% (56/128) amino acids variations including two insertions at positions 295–296 and one deletion at position 385 (Clades C and D) and one insertion at position 375 (Clade D). Variations existed in Epitopes A, B and D corresponding to GII.4 and human histo-blood group antigens binding site I in P2 subdomain. Conclusion The novel GII.17 strains that caused outbreaks in 2013–2015 may have two new variants. The evolvement of HBGAs binding site and epitopes in P2 subdomain might contribute to the novel GII.17 strains predominance in some regions.