Abstract

Evaluation of the antigenic similarity degree between the strains of the influenza virus is highly important for vaccine production. The conventional method used to measure such a degree is related to performing the immunological assays of hemagglutinin inhibition. Namely, the antigenic distance between two strains is calculated on the basis of HI assays. Usually, such distances are visualized by using some kind of antigenic cartography method. The known drawback of the HI assay is that it is rather time-consuming and expensive. In this paper, we propose a novel approach for antigenic distance approximation based on deep learning in the feature spaces induced by hemagglutinin protein sequences and Convolutional Neural Networks (CNNs). To apply a CNN to compare the protein sequences, we utilize the encoding based on the physical and chemical characteristics of amino acids. By varying (hyper)parameters of the CNN architecture design, we find the most robust network. Further, we provide insight into the relationship between approximated antigenic distance and antigenicity by evaluating the network on the HI assay database for the H1N1 subtype. The results indicate that the best-trained network gives a high-precision approximation for the ground-truth antigenic distances, and can be used as a good exploratory tool in practical tasks.

Highlights

  • The Influenza virus has a high morbidity and mortality rate, leading to about 3–5 million cases of severe illnesses, up to half a million deaths around the world annually, and high economic losses [1]

  • We propose a novel approach to approximate antigenic distances based on deep Convolutional Neural Networks (CNNs)

  • We propose a novel approach for prediction of the antigenic distance based on convolutional neural networks trained in a few-dimensional physicochemical feature space of amino acids, constituting HA sequences of the compared strains of the influenza virus

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Summary

Introduction

The Influenza virus has a high morbidity and mortality rate, leading to about 3–5 million cases of severe illnesses, up to half a million deaths around the world annually, and high economic losses [1]. The vaccination appears to be the most useful option in the struggle against the influenza virus. Despite its efficiency, this method requires permanent reviewing and updating due to continuous viral evolution [2]. There are four main types of the influenza virus, A, B, C, and D, among which A and B lead to serious public health issues. Type A is further divided into subtypes based on 18 different HA (H1-H18) and 11 different NA (N1-N11) so that, theoretically, it is 198 possible different combinations of these proteins, which enables the virus to infect a wide range of different hosts [3]. The HA protein of subtypes H1N1, H3N2, and B are considered for vaccine composition, from which H1N1 has been chosen for the current study

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