In-silico Antigenicity Determination and Clustering of Dengue Virus Serotypes

Abstract

Emerging or re-emerging dengue virus (DENV) causes dengue fever epidemics globally. Current DENV serotypes are defined based on genetic clustering, while discrepancies are frequently observed between the genetic clustering and the antigenicity experiments. Rapid antigenicity determination of DENV mutants in high-throughput way is critical for vaccine selection and epidemic prevention during early outbreaks, where accurate prediction methods are seldom reported for DENV. Here, a highly accurate and efficient in-silico model was set up for DENV based on possible antigenicity-dominant positions (ADPs) of envelope (E) protein. Independent testing showed a high performance of our model with AUC-value of 0.937 and accuracy of 0.896 through quantitative Linear Regression (LR) model. More importantly, our model can successfully detect those cross-reactions between inter-serotype strains, while current genetic clustering failed. Prediction cluster of 1,143 historical strains showed new DENV clusters, and we proposed DENV2 should be further classified into two subgroups. Thus, the DENV serotyping may be re-considered antigenetically rather than genetically. As the first algorithm tailor-made for DENV antigenicity measurement based on mutated sequences, our model may provide fast-responding opportunity for the antigenicity surveillance on DENV variants and potential vaccine study.

In SilicoAnalysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes

“…Mutations P53L, E71A, D154N, G330D, and N390S spanned residues previously implicated in diverse epitopes ( Fig. 5C ) ( 35 , 36 ). Particularly, E71A, D154N, and G330D were found mainly among WS plus SD cases, which belonged to secondary infections, or primary ones with at least 4 days of symptoms (Table S1).…”

“…5C ). Several studies had already correlated specific residues in the three domains with antibody recognition, particularly those located at the interdimer interface or the DI-DII hinge on one subunit and DIII on the other ( 33 , 35 , 36 ). Mutations P53L, E71A, D154N, G330D, and N390S spanned residues previously implicated in diverse epitopes ( Fig.…”

“…Thus, they could be thought of as variants surpassing the humoral immune barriers. On the other hand, mutations I46M, A50T, M125I, D203N, and S363A were located directly next to residues already proven to be targeted by antibodies, such as K47 ( 34 ), K124, E126, E202, K204 ( 36 ), and D362 ( 35 ), among others. In this regard, it would be likely that these substitutions arose at some point due to the antibodies’ pressures.…”

Discussion on the cultivation of college media qualified personnel in the context of new media

“…There are many problems in colleges and universities, such as lack of teachers and poor practical training results, which lead to the shortage of media personnel training and substandard quality, the disconnect between school training and media practice, and the contradiction between talent supply and demand, resulting in a greater talent gap in the media industry which is speeding up the reform [3] . The disadvantages of the traditional specialty and curriculum of media colleges and universities lead to the fact that teachers in media colleges and universities are often experts in a single media field and lack in-depth research on other media majors, especially new media.…”