Construction And Analysis Of Genomic Co-occurrence Network About GII.4Norovirus

Objective: To construct evolutionary model of GII.4Norovirus by the means ofbioinformatics and explore evolutionary mechanism and dynamics of GII.4Norovirusin the world from1974to2010, and then to find those important amino acid siteswhich affected viral evolution and to establish a foundation for preventing andcontrolling outbreak epidemics of Norovirus gastroenteritis.Methods: This topic applied primarily the method of constructing co-occurrencenucleotide network to track the evolutionary pattern of virus. We aligned233GII.4Norovirus genome sequences from1974to2010from9countries in software Muscle;And then all nucleotide positions that were conserved in all isolates from all seasonswere removed so that the nucleotide pairs that exhibited perfect co-occurrence fromall variable positions were extracted and connected, and software Cytoscape canpresent co-occurrence network and compute the topology characters of network;Co-occurring nucleotide pairs were clustered into co-occurring nucleotide modules bymeans of programming, then we analyzed each co-occurring nucleotide modules andextracted co-varying nucleotides having a synergistic effect that can reveal biologicalactivity.Results:1. The number of nucleotides variation was increasing continually along with the timeby analysing the genomic nucleotides substitution of GII.4norovirus, whichdemostrated that it was a temporal accumulation for the evolution of GII.4norovirusand viral variation still proceeded.2. The change of network connection for GII.4norovirus can mirror the alteration ofviral antigenicity quantificationally in the analysis of co-occurrence networkconnectivity. When a change peak of network connectivity occurred in some seasons, it may be a new variant or norovirus outbreak epidemics. The result of networkconnectivity was concordant with the traditional phylogenetic analysis.3. GII.4norovirus showed co-evolution in the whole genome level by the analysis ofindividual gene segments, namely, every gene segment in the genome played animproving role in the course of viral evolution.4. The relevant amino acid sites which played a key role in the process of evolutionwere extracted from every gene segment in the genome by analysing co-occurrencenucleotide modules.Conclusions:1. The nucleotide co-occurrence network model is a simple and accurate method ofcapturing viral evolutionary patterns, it can be a complement for traditionalphylogenetic analysis and provide an effective warning for the norovirus outbreakepidemics.2. And it is not just because the frequently variation in the position of the major hostreceptor binding, the evolution of GII.4norovirus is a kind of co-evolutionarybehavior in the level of genome. However, RDRP gene segment plays a little part forthe evolution.3. The amino acids which showed more co-evolution with the domain of host receptorbinding may be more important for virus evolution, and they are the mainexperimental support of site directed mutagenesis.